Dr. Joseph N. Grima
Department of Chemistry
University of Malta, Msida, MSD 06, MALTA

Syllabus:

[TOP]

1. Introduction
• Types and scales of modelling 
• Molecular modelling - the input / processing / output phases
• The concept of the potential energy surface
• Introduction to the three main types of molecular modelling methods:
• Ab initio simulations
• Semi-empirical simulations
• Empirical simulations

2. Quantum mechanical calculations 
1. Introduction
2. Aside: (Non examinable)
• Theory & concepts
• Ab inito methods
3. Semi-empirical calculations
• Methods
• Huckel methods
• NDO semi-emprirical methods: (CNDO, INDO, MINDO/3, MNDO, AM1, PM3, ZINDO/1, ZINDO/S)
• Applications of semi-empirical calculations

3. Force-field based simulations 
1. Empirical fit to the energy surface
• The energy expression
• Introduction to Valence (bond), valence cross-terms and non-bond terms in a force-field.
• Introduction to force-fields
2. A closer look at force-fields
• Types of force-fields
• A review of a few widely used force-fields
• Advantages of having several forcefields
3. A technical look force-field methods 
• Atom typing
• Charge assignment
• Functional forms
• Valence (bond) terms
• Valence cross-terms
• Non-bond tems
4. Handling non-bonded interactions
• The problem
• Number of non-bond terms
• The significance of nonbond interactions beyond the cutoff distance
• Aside - Periodic systems
• The solutions
• The step function
• The spline function
• The minimum-image convention
• Explicit-image model
• The cell multipole method (CMM)
• The Ewald model

4. Molecular Mechanics
1. Energy minimisations 
• The minimisation process
• Minimisation algorithms
• Line searches
• Steepest descent
• Conjugate gradient
• Newton- Raphson methods
• Convergence criteria
• Choosing the 'right' minimiser
2. Vibrational calculations
• Application of minimization to vibrational theory
• Theory
• Calculation of the vibrational frequencies
• Transition states
• Thermodynamic applications
• General methodology for vibrational calculations

5. Molecular Dynamics and Monte Carlo Simulations 
1. Introduction to Molecular Dynamics (MD) simulations (Deterministic approach)
• Integrators in MD Simulations
• Introduction
• Verlet integrators
• What should we look for in an integrator 
• Choosing the right time-step
• Integration Errors 
Ensembles
• The NVT ensemble 
• The NVE ensemble 
• The NPT ensemble 
• The NPH ensemble 
2. Calculation and control of Temperature
• Calculation of Temperature 
• How temperature is controlled 
• The Direct velocity scaling 
• Berendsen method of temperature-bath coupling 
3. Calculation and control of Pressure and stress
• Introduction
• Calculation of pressure and stress
• Methods of controlling pressure
4. Types of MD simulations
• Quenched dynamics
• Simulated annealing
• Consensus dynamics
• Impulse dynamics
• Langevin dynamics
• Stochastic boundary dynamics
5. General methodology for dynamics calculations
• Prerequisites 
• Stages and duration of dynamics simulations
• Equilibration stage
• Production (data-collection) stage 
• How to run a simulation
6. Monte-Carlo Methods (Stochastic approach)

6. Molecular modelling in action
1. Simulating biomolecules
2. Simulating mechanical properties
3. An evaluation of commercially available molecular modelling packages

Method of assessment:
• Course work, which may include practicals, reports and seminars (40%)
• End of year examination (60%)

Recommended texts:
1. Molecular Modelling, Principles and Applications, by Andrew R. Leach, 2nd Edition, Longman Ltd, 2000.
2. Computational Chemistry (Oxford Chemistry Primers), Guy H. Grant and W. Graham Richards, OUP, 1995.

Supplementary reading:
1. Forcefield Based Simulations (Cerius² User Guide), MSI Inc., 1997.
2. Physical Chemistry 6th ed. by P.W. Atkins, Oxford University Press