Biomolecular simulation

Some Failures and Successes of Long-Timestep Approaches to Biomolecular Simulations... 

Our work is targeted to biomolecular simulation applications, where the objective is to illuminate the structure and function of biological molecules (proteins, enzymes, etc) ranging in size from dozens of atoms to tens of thousands of atoms today, with the desire to increase this limit to millions of atoms in the near future. Such molecular dynamics (MD) simulations simply apply Newton s law to each atom in the system, with the force on each atom being determined by evaluating the gradient of the potential field at each atom s position. The potential includes contributions from bonding forces. 

Equations (l)-(3) in combination are a potential energy function that is representative of those commonly used in biomolecular simulations. As discussed above, the fonn of this equation is adequate to treat the physical interactions that occur in biological systems. The accuracy of that treatment, however, is dictated by the parameters used in the potential energy function, and it is the combination of the potential energy function and the parameters that comprises a force field. In the remainder of this chapter we describe various aspects of force fields including their derivation (i.e., optimization of the parameters), those widely available, and their applicability. 

Proper condensed phase simulations require that the non-bond interactions between different portions of the system under study be properly balanced. In biomolecular simulations this balance must occur between the solvent-solvent (e.g., water-water), solvent-solute (e.g., water-protein), and solute-solute (e.g., protein intramolecular) interactions [18,21]. Having such a balance is essential for proper partitioning of molecules or parts of molecules in different environments. For example, if the solvent-solute interaction of a glutamine side chain were overestimated, there would be a tendency for the side chain to move into and interact with the solvent. The first step in obtaining this balance is the treatment of the solvent-solvent interactions. The majority of biomolecular simulations are performed using the TIP3P [81] and SPC/E [82] water models. 

WE van Gunsteren, SR Billeter, AA Eismg, PH Hiinenberger, P Kruger, AE Mark, WRP Scott, IG Tironi. Biomolecular Simulation The GROMOS96 Manual and User Guide. Zurich BIOMOS, 1996. 

In this chapter we provide an introductory overview of the imphcit solvent models commonly used in biomolecular simulations. A number of questions concerning the formulation and development of imphcit solvent models are addressed. In Section II, we begin by providing a rigorous fonmilation of imphcit solvent from statistical mechanics. In addition, the fundamental concept of the potential of mean force (PMF) is introduced. In Section III, a decomposition of the PMF in terms of nonpolar and electrostatic contributions is elaborated. Owing to its importance in biophysics. Section IV is devoted entirely to classical continuum electrostatics. For the sake of completeness, other computational... 

B Roux, T Simonson, eds. Implicit Solvent Models for Biomolecular Simulations. Special Issue of Biophys Chem Amsterdam Elsevier, 1999. 

Case DA et al. (2005) The Amber biomolecular simulation programs. J Comput Chem 26(16) 1668-1688... 

Sagui C, Pedersen LG, Darden TA (2004) Towards an accurate representation of electrostatics in classical force fields Efficient implementation of multipolar interactions in biomolecular simulations. J Chem Phys 120 73-87... 

The total electric field, E, is composed of the external electric field from the permanent charges E° and the contribution from other induced dipoles. This is the basis of most polarizable force fields currently being developed for biomolecular simulations. In the present chapter an overview of the formalisms most commonly used for MM force fields will be presented. It should be emphasized that this chapter is not meant to provide a broad overview of the field but rather focuses on the formalisms of the induced dipole, classical Drude oscillator and fluctuating charge models and their development in the context of providing a practical polarization model for molecular simulations of biological macromolecules [12-21], While references to works in which the different methods have been developed and applied are included throughout the text, the major discussion of the implementation of these models focuses... 

One method for treating polarizability is the assignment of both partial atomic charges and induced dipoles on the atoms in a molecule. In its most common implementation in biomolecular simulations, inducible point dipoles are added to some or all atomic sites in the molecule [22-25]. An alternative methodology proposed by Allinger and co-workers is the use of bond dipoles [26],... 

Chen J, Brooks CL III, Khandogin J (2008) Recent advances in implicit solvent based methods for biomolecular simulations. Curr Opin Struct Biol 18 140-148. 

Mongan J, Case DA (2005) Biomolecular simulations at constant pH. Curr Opin Struct Biol 15 157-163. 

Wang, W. et al., Biomolecular simulations recent developments in force fields, simulations of enzyme catalysis, protein-ligand, protein-protein, and protein-nucleic acid noncovalent interactions, Annu. Rev. Biophys. Biomol. Struct. 2001, 30, 211-243... 

Bliznyuk, A. A. Rendell, A. P., Electronic effects in biomolecular simulations investigations of the KcsA potassium ion channel, J. Phys. Chem. B 2004,108, 13866-13873... 

Chung F. Wong, Tom Thacher, and Herschel Rabitz, Sensitivity Analysis in Biomolecular Simulation. 

---