This is the abstract of a talk prepared for the Oeiras Mathematical and Computational Biology Workshop. June 20, 2003, Instituto Gulbenkian de Ciência
Abstract: The standard simulation methods for biomolecular systems are essentially those originally developed for condensed phases of much simpler molecules. Adapting these methods to the biomolecular context requires a proper selection of the Hamiltonian and statistical thermodynamic ensemble that are appropriate for the biological environment.
The choice of Hamiltonian depends on the complexity of the problem being addressed. It typically ranges from molecular mechanics to simplified Hamiltonians (continuum electrostatics for multiple protonation, lattice models for folding, etc).
Conformational sampling is typically performed by molecular dynamics simulations. Although biomolecules exchange ligands with a buffered medium, the exchanging process is often too complex to be addressed with standard methods for open systems. Thus, other sampling methods must be used to address, eg, acid/base equilibrium.
Since the existing Hamiltonians and sampling methods are largely complementary, their judicious combination can produce methods for more realistic ensembles. This will be illustrated by giving an overview of some of our recent methodological developments for studying the coupling between protonation, reduction and conformation in proteins.