INTRODUCTION TO BIOMOLECULAR MODELING (BIO 181/QSB 281) SPRING 2011 INSTRUCTORS: Prof. Michael Colvin (mcolvin@ucmerced.edu) & Mr. Drew Tilley (dtilley@ucmerced.edu) COURSE GOALS AND OBJECTIVES: Molecular simulations are playing an increasing role in modern biology, from understanding protein function to designing new drugs. This course teaches the principles and practice of molecular simulation with an emphasis on the practical skills needed to perform and interpret molecular dynamics simulations of biological macromolecules. STUDENT LEARNING OUTCOMES FOR BIO181 (SEE SEPARATE SHEET FOR QSB281): By the end of this course, students will be able to: 1. Set up and run classical molecular dynamics simulations of biomolecular systems. 2. Understand the physical and statistical principles of molecular simulations. 3. Use the GROMACS suite of molecular dynamics software and molecular analysis and visualization tools 4. Build and simulate different forms of DNA double helices. 5. Understand the hierarchy of protein structure and the role of simulations predicting protein properties. 6. Locate and prepare experimental protein structures for use in molecular simulations. BIO 181/QSB 281 GENERAL COURSE LOGISTICS REQUIRED TEXT: Gromacs Users Manual Version 4.5.3: Download from http://www.gromacs.org/documentation/manual RECOMMENDED TEXTS: J.M. Haile, Molecular Dynamics Simulation: Elementary Methods, Wiley (any edition okay). K.A. Dill, Molecular Driving Forces, Garland Science (2002). COURSE WEBSITE: The BIO 181/QSB 281 website is part of the UCMCROPS course management system and will be automatically available to all students enrolled in the class under the tab S11-BIO 181 01 or S11-QSB 281 01. This UCMCROPS site contains the course announcements, electronic copies of the lecture slides and handouts, computer laboratory materials, supplementary readings, and various course-related announcements. COURSE MATERIALS & COMPUTER ACCESS: Full-size and quarter-size copies of the lecture viewgraphs will be available in Acrobat format (.pdf files) at the BIO 181 and QSB 281 UCMCROPS sites. In addition to the textbooks and class handouts, a computer and internet access will be required for this class. For students who do not otherwise have access to a computer or the internet, computers will be available at several campus locations including the main reading room in the library. LECTURES: Tuesday and Thursday, 4:30-5:45PM, Room 263, Classroom Building. LABORATORY/ DISCUSSION SESSIONS: Tuesday 6:00-9:50PM (SE138). OFFICE HOURS: To be scheduled in first week of class. GRADING: See separate sections for BIO 181 and QSB 281 below COMPUTER LABORATORIES: There are eleven computer laboratory assignments for BIO 181 and QSB 281. Attendance in the laboratory sections is mandatory to receive credit for the lab. Lab write ups are due by midnight the Monday the week after you do the lab (the second Monday for 2-week labs). MIDTERM AND FINAL EXAMS: There will be one in-class midterm exam and a three-hour Final Exam. 1
BIO 180 SPECIFIC LOGISTICS: OFFICE HOURS: Prof. Colvin and Mr. Tilley will schedule these during the first week of class. COURSE POINTS: Grades will be based upon points received for the lecture quizzes, the laboratories, the midterm exams, and the final exam, based on the following scales. Activity Number % Final Grade Laboratories/ ~10 20%* Discussions Lecture quizzes ~20 5% Midterm Exam 1 35% Final Exam 1 40% Total 100% *You must get at least 50% of the points on 6 of the 10 labs (lab 0 not counted) to get a passing grade in the class. LETTER GRADES: The final distribution of grades in BIO 181 will depend on the overall achievement of the students in the course, but the following grades will be guaranteed to students achieving the indicated percentage of the total possible points in the course Grade % of total points achieved A (A-, A, or A+) Over 85% B (B-, B, or B+) Over 75% C (C-, C, or C+) Over 65% D (D-, D, or D+) Over 55% Information on grade appeals, incompletes, etc. can be found at the end of this document and in the UC Merced Grading Policy available from the Registrar (http://registrar.ucmerced.edu/policies/grades). 2
QSB 281 SPECIFIC LOGISTICS: This course shares lectures and laboratories with the upper division course BIO 181. QSB 281 will also share the midterm and final exams with BIO 181. The major differences between QSB 281 and BIO 181 are the higher level of expertise expected of the graduate participants, a separate discussion session, and additional assignments (See below). PREREQUISITES: Graduate Standing DISCUSSION SESSION: A one-hour discussion with Prof. Colvin will be scheduled during the first week. LABORATORY SESSIONS: Tuesday 6:00-9:50PM (SE138). OFFICE HOURS: Office hours with Prof. Colvin can be scheduled as needed. PROJECTS & HOMEWORK: QSB 281 requires two class projects in molecular dynamics and a series of homework assignments based readings in the current biomolecular simulation literature. Ideally, the projects will be directly related to each student s graduate research. Each project will involve a short powerpoint presentation to the instructor and other graduate students in QSB 281. COURSE POINTS: Grades will be based upon points received for the projects, homeworks, midterms, and final exam, based on the following scale. Activity Number Percentage of Final Grade Laboratories ~10 15% Projects/Homeworks ~5 10% Lecture quizzes ~20 2% Midterm Exam 1 33% Final Exam 1 40% Total 100% LETTER GRADES: The final distribution of grades in QSB 281 will depend on the overall achievement of the students in the course, but the following grades will be guaranteed to students achieving the indicated percentage of the total possible points in the course Grade % of total points achieved A (A-, A, or A+) Over 90% B (B-, B, or B+) Over 80% C (C-, C, or C+) Over 70% D (D-, D, or D+) Over 60% Information on grade appeals, incompletes, etc. can be found at the end of this document and in the UC Merced Grading Policy available from the Registrar (http://registrar.ucmerced.edu/policies/grades). 3
STUDENT SERVICES: UC Merced is committed to make our courses accessible to all students, including students with limited mobility, impaired hearing or vision, and learning disabilities. Students with special needs should contact their advisor as early as possible in the semester so that appropriate arrangements can be made. The American with Disabilities Act (ADA) is a federal anti-discrimination statute that provides comprehensive civil rights protection for persons with disabilities. Among other things, this legislation requires all students with disabilities be guaranteed a learning environment that provides for reasonable accommodation of their disabilities. If you believe you have a disability requiring an accommodation, please contact the Disability Services Center: http://disability.ucmerced.edu/. MISSED EXAMS Make-up exams will be offered for the midterm only on the condition that students who miss the midterm provide documentation for one of two acceptable excuses: Incapacitating illness or accident requires a note from student s physician (not a family member) or from UC Merced Health Services. Death or serious illness of an immediate family member requires proper documentation. Students who miss the final exam will receive a grade of F for the course unless an acceptable excuse is provided (see above) and the student was achieving a passing grade (C- or better) in all course work up until the final exam. Students who have a documented reason, such as a religious observance, a scheduling conflict with another exam, or other academic or professional activity (e.g. graduate school interview) may request to take the midterm exam before the scheduled exam time. Students taking an exam early may not discuss any aspect of the exam with other students in the class, to do so is a serious breach of academic integrity (see below). Students seeking to reschedule an exam should contact the instructor as early as possible, ideally during the first two weeks of the semester. EXAM REGRADING Midterm exams may be submitted for regrading if the student believes that errors were made in the grading. Requests for regrading must be made within a week of the exam being returned. Exams submitted for regrading will be completely regraded, so that the resulting grade may be higher or lower than the original grade. A random sample of all midterm exams will be photocopied after the initial grading. If a comparison of the photocopy and the exam submitted for regrading indicates any alteration, the case will be forwarded to the Office of Judicial Affairs. The final exam will not be returned to the students, but a student may request to examine the graded final in the presence of the instructor after the end of the semester. LATE ASSIGNMENTS: Computational laboratories or homeworks turned in after their due date will automatically have a fraction of the total point possible point value deducted. There will be a penalty of 25% deducted for every week after the due date and no assignments will be accepted more than 2 weeks late. The only exceptions will in the case of documented acceptable excuses (see Missed Exams section). ACADEMIC INTEGRITY: You are not allowed to work with another person on homework or laboratory assignments for this class. At the first instance of copied answers on assignments, a grade penalty greater that the point value of the assignment will be given to students with duplicate answers. Subsequent copied assignments may be forwarded to the Vice-Chancellor for Undergraduate Affairs and the Office for Judicial Affairs and could lead to dismissal from course or university (see section on Academic Integrity below). 4
Academic integrity is the foundation of an academic community and without it none of the educational or research goals of the university can be achieved. All members of the university community are responsible for its academic integrity. Existing policies forbid cheating on examinations, plagiarism and other forms of academic dishonesty. The current policies for UC Merced are described in the UC Merced Interim Academic Honesty Policy and Adjudication Procedures available from your instructor. The following general guidelines are adapted from UC Davis Code of Academic Conduct (http://sja.ucdavis.edu/): Examples of academic dishonesty include: receiving or providing unauthorized assistance on examinations using unauthorized materials during an examination plagiarism - using materials from sources without citations altering an exam and submitting it for re-grading fabricating data or references using false excuses to obtain extensions of time or to skip coursework The ultimate success of a code of academic conduct depends largely on the degree to which the students fulfill their responsibilities towards academic integrity. These responsibilities include: Be honest at all times. Act fairly toward others. For example, do not disrupt or seek an unfair advantage over others by cheating, or by talking or allowing eyes to wander during exams. Take group as well as individual responsibility for honorable behavior. Collectively, as well as individually, make every effort to prevent and avoid academic misconduct, and report acts of misconduct which you witness. Do not submit the same work in more than one class. Unless otherwise specified by the instructor, all work submitted to fulfill course requirements must be work done by the student specifically for that course. This means that work submitted for one course cannot be used to satisfy requirements of another course unless the student obtains permission from the instructor. Unless permitted by the instructor, do not work with others on graded coursework, including in class and take-home tests, papers, or homework assignments. When an instructor specifically informs students that they may collaborate on work required for a course, the extent of the collaboration must not exceed the limits set by the instructor. Know what plagiarism is and take steps to avoid it. When using the words or ideas of another, even if paraphrased in your own words, you must cite your source. Students who are confused about whether a particular act constitutes plagiarism should consult the instructor who gave the assignment. Know the rules. Those who violate campus rules regarding academic misconduct are subject to disciplinary sanctions, including suspension and dismissal. 5
BIO181/QSB 281 Biomolecular Modeling--Syllabus, Spring 2011 Session Week Date Topics Lecture 1 1 1/18/11 Course logistics, introduction to molecular dynamics, molecular units and timescales Lecture 2 1 1/20/11 Energies, Equations of motion, trajectories, phase space, mixing -- 2 1/25/11 No Lecture LAB 0 2 1/25/11 Linux basics and remote computing Lecture 3 2 1/27/11 Temperature, velocity distributions, elements of an MD simulation, laboratories -- 3 2/1/11 No Lecture LAB 1 3 2/1/11 Kinetic Theory of gases Lecture 4 3 2/3/11 Numerical integrations, equations of state Lecture 5 4 2/8/11 Using GROMACS LAB 2 4 2/8/11 GROMACS basics and argon equation of state Lecture 6 4 2/10/11 Entropy, thermodynamic ensembles, thermostats & barostats Lecture 7 5 2/15/11 Transport properties, Einstein relation, velocity autocorrelation functions LAB 3 5 2/15/11 Argon transport properties and alternate ensemble simulations Lecture 8 5 2/17/11 Noble gas Lennard-Jones potentials, radial distribution functions, phase changes Lecture 9 6 2/22/11 Sampling statistics, probability distributions, expected values, block averages LAB 4 6 2/22/11 Noble gas phase transitions Lecture 10 6 2/24/11 Chemical bonds, molecular force fields, challenges in molecular simulations Lecture 11 7 3/1/11 Properties of water, water models, hydrogen bonds LAB 5 7 3/1/11 Basics of molecular simulations, water transport properties Lecture 12 7 3/3/11 Heat capacities and phase transitions in water Lecture 13 8 3/8/11 Ionic solutions, molecular graphics LAB 6 (1) 8 3/8/11 Simulations of ionic solutions (part 1) Lecture 14 8 3/10/11 Simulation of macromolecules, visualization, energy minimization, constraints Midterm Exam 9 3/15/11 Midterm covering principles of MD Simulations (Lectures 1-13) LAB 6 (2) 9 3/15/11 Simulations of ionic solutions (part 2) Lecture 15 9 3/17/11 DNA structure and dynamics -- 10 3/22 & 24/11 Spring Break: No lectures or Labs -- 11 3/29/11 No Lecture LAB 7 11 3/29/11 Basics of DNA simulation and structural analysis Lecture 16 11 3/31/11 Cutoffs and long-range electrostatics, trade-offs in MD accuracy Lecture 17 12 4/5/11 Building DNA structures, DNA mutations LAB 8 (1) 12 4/5/11 Simulations of DNA mismatch mutations (part 1) Lecture 18 12 4/7/11 Levels of protein structure and tools for protein simulation Lecture 19 13 4/12/11 Tools for analyzing protein structures and motions LAB 8 (2) 13 4/12/11 Simulations of DNA mismatch mutations (part 2) Lecture 20 13 4/14/11 Designing & setting up protein MD simulations Guest Lecture 1 14 4/19/10 Guest lecture Biological MD Applications LAB 9 14 4/19/10 Basics of protein simulation and structural analysis -- 14 4/21/11 No Lecture Lecture 21 15 4/26/11 Protein thermostability and protein mutations LAB 10 (1) 15 4/26/11 Simulations of protein thermostability (part 1) Lecture 22 15 4/28/11 Acceleration techniques: Annealing and replica exchange Lecture 23 16 5/3/11 Coarse-grained models and homology-based protein structure prediction LAB 10 (2) 16 5/3/11 Simulations of protein thermostability (part 2) Lecture 24 16 5/5/11 Future challenges and promise of biomolecular simulations. Review of key concepts. Final Exam 16 5/7/11 Saturday Final Exam 3:00-6:00 PM COB 263
LEARNING OUTCOMES INTRODUCTION TO BIOMOLECULAR MODELING (BIO 181/QSB 281) SPRING 2011 INSTRUCTORS: Prof. Michael Colvin (mcolvin@ucmerced.edu) & Mr. Drew Tilley (dtilley@ucmerced.edu) COURSE GOALS AND OBJECTIVES: Molecular simulations are playing an increasing role in modern biology, from understanding protein function to designing new drugs. This course teaches the principles and practice of molecular simulation with an emphasis on the practical skills needed to perform and interpret molecular dynamics simulations of biological macromolecules. STUDENT LEARNING OUTCOMES: By the end of this course, students will be able to: 1. Set up and run classical molecular dynamics simulations of biomolecular systems. 2. Understand the physical and statistical principles of molecular simulations. 3. Use the GROMACS suite of molecular dynamics software and molecular analysis and visualization tools 4. Build and simulate different forms of DNA double helices. 5. Understand the hierarchy of protein structure and the role of simulations predicting protein properties. 6. Locate and prepare experimental protein structures for use in molecular simulations. These learning outcomes map onto the class lectures and computer laboratories as follows: Session Topics 1 2 3 4 5 6 Lecture 1 Lecture 2 Lecture 3 Course logistics; introduction to molecular dynamics, molecular units and timescales Energies, Equations of motion, trajectories, phase space, mixing Temperature, velocity distributions, elements of an MD simulation, laboratories LAB 1 Linux Basics and Kinetic Theory of Gases Lecture 4 Numerical integrations, equations of state. Lecture 5 Using GROMACS X LAB 2 GROMACS basics and Argon Equation of State X Lecture 6 Lecture 7 LAB 3 Lecture 8 Entropy, thermodynamic ensembles, thermostats & barostats Transport properties, Einstein relation, velocity autocorrelation functions Argon Transport Properties and Alternate Ensemble simulations X Noble gas Lennard-Jones potentials, radial distribution functions, phase changes LAB 4 Noble gas phase transitions X Lecture 9 Lecture 10 Sampling statistics, probability distributions, expected values, block averages Chemical bonds, molecular force fields, challenges in molecular simulations Lecture 11 Properties of water, water models, hydrogen bonds 1
LAB 5 Basics of molecular simulations, water transport properties X Lecture 12 Heat capacities and phase transitions in water Lecture 13 Ionic solutions, molecular graphics LAB 6 Simulations of ionic solutions X Lecture 14 Lecture 15 Simulation of macromolecules, visualization, energy minimization, constraints X Cutoffs and long-range electrostatics, trade-offs in MD accuracy Lecture 16 DNA structure and dynamics LAB 7 Basics of DNA simulation and structural analysis X Lecture 17 Building DNA structures, DNA visualization and analysis tools LAB 8 Simulations of DNA mismatch mutations X Lecture 18 Molecular dynamics acceleration and annealing techniques Lecture 19 Levels of protein structure and folding dynamics Lecture 20 Tools for comparing protein structures Lecture 21 Protein thermostability and protein mutations LAB 9 Simulations of protein thermostability (part 1) X Lecture 22 Lecture 23 Acceleration techniques: Annealing and replica exchange X Coarse-grained models and homology-based protein structure prediction X LAB 10 Simulations of protein thermostability (part 2) X Lecture 24 Future challenges and promise of biomolecular simulations. Review of key concepts. 2
BIO 181/QSB 281 GENERAL COURSE LOGISTICS REQUIRED TEXT: Gromacs Users Manual Version 4. Download from http://www.gromacs.org/documentation/manual RECOMMENDED TEXTS: J.M. Haile, Molecular Dynamics Simulation: Elementary Methods, Wiley (any edition okay). K.A. Dill, Molecular Driving Forces, Garland Science (2002). COURSE WEBSITE: The BIO 181/QSB 281 website is part of the UCMCROPS course management system and will be automatically available to all students enrolled in the class under the tab S10-BIO 181 01 or S10-QSB 281 01. This UCMCROPS site contains the course announcements, electronic copies of the lecture slides and handouts, computer laboratory materials, supplementary readings, and various course-related announcements. COURSE MATERIALS & COMPUTER ACCESS: Full-size and quarter-size copies of the lecture viewgraphs will be available in Acrobat format (.pdf files) at the BIO 181 and QSB 281 UCMCROPS sites. In addition to the textbooks and class handouts, a computer and internet access will be required for this class. For students who do not otherwise have access to a computer or the internet, computers will be available at several campus locations including the main reading room in the library. LECTURES: Monday and Wednesday, 3:00-4:15, Room 267, Classroom Building. LABORATORY SESSIONS: Section 2C: W 5:00-7:50 (SE100), Section 3C: R 10:30-1:20 (SE 138). DISCUSSIONS AND OFFICE HOURS: See separate sections for BIO 181 and QSB 281 below GRADING: See separate sections for BIO 181 and QSB 281 below COMPUTER LABORATORIES: There are ten computer homework assignments for BIO 181 and QSB 281. Attendance in the laboratory sections is mandatory to receive credit for the lab. Lab write ups are due by midnight the Tuesday the week after you do the lab (the second Tuesday for 2-week labs). MIDTERM AND FINAL EXAMS: There will be one in-class midterm exam and a three-hour Final Exam. 3
BIO 180 SPECIFIC LOGISTICS: DISCUSSION SESSIONS: Section 2C: W 8:00-8:50 (SE138), Section 3C: R 9:30-10:20 (SE 138). LABORATORY SESSIONS: Section 2C: W 5:00-7:50 (SE100), Section 3C: R 10:30-1:20 (SE 138). OFFICE HOURS: Prof. Colvin and Mr. Phillips will schedule these during the first week of class. COURSE POINTS: Grades will be based upon points received for the lecture quizzes, the laboratories, the midterm exams, and the final exam, based on the following scales. Activity Number % Final Grade Laboratories/ ~10 20% Discussions Lecture quizzes ~20 5% Midterm Exam 1 35% Final Exam 1 40% Total 100% LETTER GRADES: The final distribution of grades in BIO 181 will depend on the overall achievement of the students in the course, but the following grades will be guaranteed to students achieving the indicated percentage of the total possible points in the course Grade % of total points achieved A (A-, A, or A+) Over 85% B (B-, B, or B+) Over 75% C (C-, C, or C+) Over 65% D (D-, D, or D+) Over 55% Information on grade appeals, incompletes, etc. can be found in the UC Merced Grading Policy available from the Registrar (http://registrar.ucmerced.edu/policies/grades). 4
STUDENT SERVICES: UC Merced is committed to make our courses accessible to all students, including students with limited mobility, impaired hearing or vision, and learning disabilities. Students with special needs should contact their advisor as early as possible in the semester so that appropriate arrangements can be made. The American with Disabilities Act (ADA) is a federal anti-discrimination statute that provides comprehensive civil rights protection for persons with disabilities. Among other things, this legislation requires all students with disabilities be guaranteed a learning environment that provides for reasonable accommodation of their disabilities. If you believe you have a disability requiring an accommodation, please contact the Disability Services Center: http://disability.ucmerced.edu/. MISSED EXAMS Make-up exams will be offered for the midterm only on the condition that students who miss the midterm provide documentation for one of two acceptable excuses: Incapacitating illness or accident requires a note from student s physician (not a family member) or from UC Merced Health Services. Death or serious illness of an immediate family member requires proper documentation. Students who miss the final exam will receive a grade of F for the course unless an acceptable excuse is provided (see 1 & 2 above) and the student was achieving a passing grade (C- or better) in all course work up until the final exam. Students who have a documented reason, such as a religious observance, a scheduling conflict with another exam, or other academic or professional activity (e.g. graduate school interview) may request to take the midterm exam before the scheduled exam time. Students taking an exam early may not discuss any aspect of the exam with other students in the class, to do so is a serious breach of academic integrity (see below). Students seeking to reschedule an exam should contact the instructor as early as possible, ideally during the first two weeks of the semester. EXAM REGRADING Midterm exams may be submitted for regrading if the student believes that errors were made in the grading. Requests for regrading must be made within a week of the exam being returned. Exams submitted for regrading will be completely regraded, so that the resulting grade may be higher or lower than the original grade. A random sample of all midterm exams will be photocopied after the initial grading. If a comparison of the photocopy and the exam submitted for regrading indicates any alteration, the case will be forwarded to the Office of Judicial Affairs. The final exam will not be returned to the students, but a student may request to examine the graded final in the presence of the instructor after the end of the semester. LATE ASSIGNMENTS: Computational laboratories or homeworks turned in after their due date will automatically have a fraction of the total point possible point value deducted. There will be a penalty of 25% deducted for every week after the due date and no assignments will be accepted more than 2 weeks late. The only exceptions will in the case of documented acceptable excuses (see Missed Exams section). ACADEMIC INTEGRITY: You are not allowed to work with another person on answers except for the specific case of team computer laboratories described above. At the first instance of copied answers on assignments, no credit will be given to all students with duplicate answers & the assignments will be forwarded to the Vice-Chancellor for Undergraduate Affairs and the Office for Judicial Affairs. Subsequent copied assignments could lead to dismissal from course or university (see section on Academic Integrity below). 5
Academic integrity is the foundation of an academic community and without it none of the educational or research goals of the university can be achieved. All members of the university community are responsible for its academic integrity. Existing policies forbid cheating on examinations, plagiarism and other forms of academic dishonesty. The current policies for UC Merced are described in the UC Merced Interim Academic Honesty Policy and Adjudication Procedures available from your instructor. The following general guidelines are adapted from UC Davis Code of Academic Conduct (http://sja.ucdavis.edu/): Examples of academic dishonesty include: receiving or providing unauthorized assistance on examinations using unauthorized materials during an examination plagiarism - using materials from sources without citations altering an exam and submitting it for re-grading fabricating data or references using false excuses to obtain extensions of time or to skip coursework The ultimate success of a code of academic conduct depends largely on the degree to which the students fulfill their responsibilities towards academic integrity. These responsibilities include: Be honest at all times. Act fairly toward others. For example, do not disrupt or seek an unfair advantage over others by cheating, or by talking or allowing eyes to wander during exams. Take group as well as individual responsibility for honorable behavior. Collectively, as well as individually, make every effort to prevent and avoid academic misconduct, and report acts of misconduct which you witness. Do not submit the same work in more than one class. Unless otherwise specified by the instructor, all work submitted to fulfill course requirements must be work done by the student specifically for that course. This means that work submitted for one course cannot be used to satisfy requirements of another course unless the student obtains permission from the instructor. Unless permitted by the instructor, do not work with others on graded coursework, including in class and take-home tests, papers, or homework assignments. When an instructor specifically informs students that they may collaborate on work required for a course, the extent of the collaboration must not exceed the limits set by the instructor. Know what plagiarism is and take steps to avoid it. When using the words or ideas of another, even if paraphrased in your own words, you must cite your source. Students who are confused about whether a particular act constitutes plagiarism should consult the instructor who gave the assignment. Know the rules. Those who violate campus rules regarding academic misconduct are subject to disciplinary sanctions, including suspension and dismissal. 6