Forcefield Based Simulations

      Contents

Release 4.5 June 2000

1. Introduction

Who should use this documentation

What can simulation engines do?

Energy minimization

Molecular dynamics

Other forcefield-based calculations

What are forcefields and simulation engines?

Using this guide

Additional information

Typographical conventions

2. Forcefields

The potential energy surface

Empirical fit to the potential energy surface

The forcefield

The energy expression

Forcefields supported by MSI forcefield engines

Main types of forcefields

Advantages of having several forcefields

Primary uses of each MSI forcefield

Second-generation forcefields accurate for many properties

CFF91, PCFF, CFF, COMPASS--consistent forcefields

MMFF94 and MMFF94s, the Merck molecular forcefield

Rule-based forcefields broadly applicable to the periodic table

ESFF, extensible systematic forcefield

UFF, universal forcefield

VALBOND

Dreiding forcefield

Classical forcefields

AMBER forcefield

CHARMm forcefield

CVFF, consistent valence forcefield

Special-purpose forcefields

Glass forcefield

MSXX forcefield for polyvinylidene fluoride

Zeolite forcefields

Forcefields for sorption on zeolites

Forcefields for Cerius2·Morphology module

Archived and untested forcefields

3. Preparing the Energy Expression and the Model

Using forcefields

Selecting forcefields

Assigning forcefield atom types and charges

What are atom types in forcefields?

Assigning atom types to a model

Assigning charges

Parameter assignment

Determination of which parameters are used with which atom types

Automatic assignment of values for missing parameters

Manual parameter assignment

Using alternative forms of energy terms

Removing terms from the energy expression

Scaling or editing any selected type of term

Alternative bond terms

Scaled torsion terms

Inversion terms

Nonbond functional form

Hydrogen bonds and hydrogen-bond terms

Bond-angle cross terms vs. Urey-Bradley terms

Applying constraints and restraints

When to use constraints/restraints

Fixed atom constraints

Template forcing, tethering, quartic droplet restraints, and consensus conformations

General internal-coordinate restraints

Distance and NOE restraints

Distance and angle constraints in dynamics simulations

Angle restraints

Torsion restraints

Inversion, out-of-plane, and chiral restraints

Plane and other geometrical constraints and restraints

Modeling periodic systems

Minimum-image model

Explicit-image model

Crystal simulations

Bonds across boundaries

Handling nonbond interactions

Combination rules for van der Waals terms

The dielectric constant and the Coulombic term

Nonbond cutoffs

Cell multipole method

Ewald sums for periodic systems

4. Minimization

General minimization process

Specific minimization example

Line search

Minimization algorithms

Steepest descents

Conjugate gradient

Newton-Raphson methods

General methodology for minimization

Minimizations with MSI simulation engines

When to use different algorithms

Convergence criteria

Significance of minimum-energy structure

Energy and gradient calculation

Vibrational calculation

Application of minimization to vibrational theory

Vibrational frequencies

General methodology for vibrational calculations

5. Molecular Dynamics

Integration algorithms

Introduction

Criteria of good integrators in molecular dynamics

Integrators in MSI simulation engines

The choice of timestep

Integration errors

Example 1--Two colliding hydrogen atoms

Example 2--Energy conservation of a harmonic oscillator

Statistical ensembles

NVE ensemble

NVT ensemble

NPT and NST ensembles

NPH and NSH ensembles

Equilibrium thermodynamic properties

Temperature

How temperature is calculated

How temperature is controlled

Pressure and stress

Units and sign conventions for pressure and stress

How pressure and stress are calculated

How pressure and stress are controlled

Types of dynamics simulations

Quenched dynamics

Simulated annealing

Consensus dynamics

Impulse dynamics

Langevin dynamics

Stochastic boundary dynamics

Multibody order-N dynamics

Constraints during dynamics simulations

The SHAKE algorithm

The RATTLE algorithm

Dynamics trajectories

General methodology for dynamics calculations

Stages and duration of dynamics simulations

Dynamics with MSI simulation engines

Restarting a dynamics simulation

6. Free Energy

Relative free energy--theory and implementation

Finite difference thermodynamic integration (FDTI)

Relative free energy--methodology

Absolute free energy

Theory and implementation

Example: Fentanyl

Analysis of results

A. References

B. Forcefield Terms and Atom Types

Forcefield term definitions

AMBER atom types

Standard AMBER forcefield

Homan's carbohydrate forcefield

CFF91 atom types

CHARMm atom types

COMPASS atom types

CVFF atom types

CVFF_aug atom types

ESFF atom types

PCFF--additional atom types