Download presentation

Presentation is loading. Please wait.

Published byZoie Carrier Modified over 3 years ago

1
Crystallography, Birkbeck MOLECULAR SIMULATIONS ALL YOU (N)EVER WANTED TO KNOW Julia M. Goodfellow Dynamic Processes: Lecture 1 Lecture Notes

2
Crystallography, Birkbeck WHY DO SIMULATIONS? Numerical simulations fall between experiments and theoretical methods n Where there are no available experimental data n Where it is difficult or impossible to get exptl data n Add atomic insight

3
Crystallography, Birkbeck AIMS AND OBJECTIVES n Please see overview of the course on ‘Dynamic Processes’ which lists the aims and objectives of this course unit and each letter

4
Crystallography, Birkbeck What is molecular simulation/modelling ? n Quantum Mechanical Methods n Knowledge based methods n Classical Methods based on concept of energy function describing interaction between atoms

5
Crystallography, Birkbeck CONFORMATION n EXPERIMENTAL ANALYSIS (1) X-RAY refinement (2) NMR - structure determination from NOEs. n HOMOLOGY MODELLING Optimization of models n ‘ENERGY’ CALCULATIONS (1) conformation in solution (2) conformation of complex

6
Crystallography, Birkbeck DYNAMICS n Multiple Conformations n rms - atomic fluctuations n occurrence of hydrogen bonds n anisotropic thermal elipsoids n correlation functions

7
Crystallography, Birkbeck THERMODYNAMICS n POTENTIAL ENERGY n FREE ENERGY CHANGE n RELATIVE BINDING ENERGY n STABILITY OF CHEMICAL MODIFICATION n PARTITION COEFFICIENTS n REDOX POTENTIALS

8
Crystallography, Birkbeck Methods n Energy Minimization: based on using mathematical methods to optimize a function to its minimum value n Monte Carlo: based on probability of change in energy between different conformations n Molecular Dynamics: based on Newton’s Laws of Motion

9
Crystallography, Birkbeck MONTE CARLO SIMULATIONS n one could make random moves, calculate energy, add energy* probability to get average n instead make random move and choose whether to accept according to probability and then just add energies n state n, make random move to n’ n DEnn’ = En’ - En n If DEnn’ < 0, Accept n If DEnn’ > 0, make choice as follows: –choose random nos x 0

10
Crystallography, Birkbeck Molecular Dynamics n Uses time trajectory as systems evolves due to Newton’s Laws of Motion n F = M x A n know mass & calculate force from derivative of potential energy, so get acceleration A n a = dV/dt where v is velocity n v = dx/dt where x is position n Solve differential equations numerically using standard methods Verlet, Beeman, Gear n solutions are iterative over small time steps typically 1 fs; n generates trajectory through microstates which obey ensemble constraint (NVT) and hence one can calculate averages

11
Crystallography, Birkbeck Non-standard techniques n ‘simulated annealing’ uses MC or MD at high temperature to move over energy barriers to allow conformational change followed by cooling/min into energy minimum n ‘free energy’ calculations n non-equilibrium systems n joint QM/MD calculations

12
Crystallography, Birkbeck STATISTICAL MECHANICS link between atomistic representation ( x,y,z,vx,vy,vz) and thermodynamics ( macroscopic parameters such as heat capacity) For many body systems - lots of microstates consistent with a given set of conditions (Temp, Pressure, Volume, Natoms) Experimental measurements are an average over these states. Simulations - find trajectory through all possible states and calculate average

13
Crystallography, Birkbeck FORCE FIELDS n What interactions are important ? n How do you represent them ? n How do you parameterize them ? Bond deformation, Bond Angle deform., Torsion angles, improper torsion, cross-terms van der Waals, electrostatics, 1-4 electrostatics hydrogen bonding Solvent

14
Crystallography, Birkbeck Software and hardware n Software: lots - amber, insight/discover, sybyl, quanta/charmm etc n Hardware: PC to CRAY T3D n Requirements: Initial Model/Set Up Running Simulation Analysis and Validation

15
Crystallography, Birkbeck initial requirements n Starting configuration of atoms n info about the molecule - nos of atoms, atom types, connectivity (bonds, angles, torsions), partial electronic charge n info about how atoms interact - covalent bonds, angles and torsions: non-covalent LJ, electrostatics, H-bond n Solvent ? n control: Vol, P, Temp, time step

16
Crystallography, Birkbeck VALIDATION n Everyone gets good qualitative agreement with experimental data n Totally ad hoc n choose sensible starting model n check that it is behaving properly especially at the beginning n thorough analysis of many parameters - even if you cannot publish them all n choose the right level of detail

17
Crystallography, Birkbeck Future - n improve assumptions n validation n need to improve - long range and short range electrostatics n need to improve precision of all interactions as compromise between many weak interactions n need to increase time beyond ns to ms n Need to get quicker so that we can ‘play’ with system. difficult when it takes 3-6 months a calculation

18
Crystallography, Birkbeck ATOMISTIC SIMULATIONS n APPLICATION AREAS (A) environmental effects on peptide stability: role of solvents in stabilising/ destabilising secondary structure (B) conformation of chemically modified dnas n NOVEL ALGORITHMS Protein folding/unfolding - solvent insertion into cavities; stability and unfolding of different protein architecture n VALIDATION development of systematic protocols for assessing simulations

Similar presentations

OK

Computational Biology BS123A/MB223 UC-Irvine Ray Luo, MBB, BS.

Computational Biology BS123A/MB223 UC-Irvine Ray Luo, MBB, BS.

© 2017 SlidePlayer.com Inc.

All rights reserved.

Ads by Google

Ppt on printed circuit board Ppt on home security system using microcontroller Class 7 science ppt on light Ppt on do's and don'ts of group discussion images Ppt on teachers day greeting Ppt on product advertising photography Ppt on natural and artificial satellites in space Ppt on conservation of wildlife and natural vegetation types Ppt online open port Ppt on tcp ip protocol chart