Proteins computer simulation

Devising force fields in terms of reduced descriptions of the protein conformation has therefore been a recurring theme in protein computer simulations and structure prediction. It received a new impetus recently with the realization that the body of protein sequence and structure data has probably reached a sufficient size to derive from it effective potentials, which provide an intermediate description between those given by detailed atomic force fields and residue-specific secondary structures. In recent years, a large number of studies has been devoted to this issue.This article reviews these developments, with emphasis on the force fields derived from statistical analyses of known protein structures, also referred to as statistical, database, or knowledge-based potentials. 

Nada, H. and Fumkawa, Y. (2012) Antifreeze proteins computer simulation studies on the mechanism of ice growth inhibition. Polym. J., 44 (7), 690-698. 

Taketomi H, Ueda Y and Go N 1975 Studies on protein folding, unfolding, and fluctuations by computer simulation Int. J. Pept. Protein Res. 7 445-59... 

Northrup S H and Erickson H P 1992 Kinetics of protein-protein association explained by Brownian dynamics computer simulation Proc. Natl Acad. Sci. USA 89 3338-42... 

Guenot, J., Kollman, P.A. Conformational and energetic effects of truncating nonbonded interactions in an aqueous protein dynamics simulation. J. Comput. Chem. 14 (1993) 295-311. 

Elamrani et al. 1996] Elamrani, S., Berry, M.B., Phillips Jr., G.N., McCammon, J.A. Study of Global Motions in Proteins by Weighted Masses Molecular Dynamics Adenylate Kinase as a Test Case. Proteins 25 (1996) 79-88 [Elcock et al. 1997] Elcock, A.H., Potter, M.J., McCammon, J.A. Application of Poisson-Boltzmann Solvation Forces to Macromolecular Simulations. In Computer Simulation of Biomoleeular Systems, Vol. 3, A.J. Wilkinson et al. eds., ESCOM Science Publishers B.V., Leiden... 

M. Levitt and A. Warshel, Computer simulation of protein folding. Nature 253 (1975), 694-698. 

The current understanding of the protein folding process has benefited much from studies that focus on computer simulations of simplified lattice models. These studies try to construct as simple a model as possible that will capture some of the more important properties of the real polypeptide chain. Once such a model is defined it can be explored and studied at a level of detail that is hard to achieve with more realistic (and thus more complex) atomistic models. 

H Taketomi, Y Ueda, N Go. Studies on protein folding, unfolding and fluctuations by computer simulation. 1. The effect of specific ammo acid sequence represented by specific mter-umt interactions. Int J Peptide Protein Res 7 445-459, 1975. 

Computer simulations of electron transfer proteins often entail a variety of calculation techniques electronic structure calculations, molecular mechanics, and electrostatic calculations. In this section, general considerations for calculations of metalloproteins are outlined in subsequent sections, details for studying specific redox properties are given. Quantum chemistry electronic structure calculations of the redox site are important in the calculation of the energetics of the redox site and in obtaining parameters and are discussed in Sections III.A and III.B. Both molecular mechanics and electrostatic calculations of the protein are important in understanding the outer shell energetics and are discussed in Section III.C, with a focus on molecular mechanics. 

S. C. Ke, L. J. DeLucas, J. G. Harrison. Computer simulation of protein crystal growth using aggregates as the growth unit. J Phy D 57 1064, 1998. 

A complete set of intermolecular potential functions has been developed for use in computer simulations of proteins in their native environment. Parameters have been reported for 25 peptide residues as well as the common neutral and charged terminal groups. The potential functions have the simple Coulomb plus Lennard-Jones form and are compatible with the widely used models for water, TIP4P, TIP3P and SPC. The parameters were obtained and tested primarily in conjunction with Monte Carlo statistical mechanics simulations of 36 pure organic liquids and numerous aqueous solutions of organic ions representative of subunits in the side chains and backbones of proteins... 

The use of computer simulations to study internal motions and thermodynamic properties is receiving increased attention. One important use of the method is to provide a more fundamental understanding of the molecular information contained in various kinds of experiments on these complex systems. In the first part of this paper we review recent work in our laboratory concerned with the use of computer simulations for the interpretation of experimental probes of molecular structure and dynamics of proteins and nucleic acids. The interplay between computer simulations and three experimental techniques is emphasized (1) nuclear magnetic resonance relaxation spectroscopy, (2) refinement of macro-molecular x-ray structures, and (3) vibrational spectroscopy. The treatment of solvent effects in biopolymer simulations is a difficult problem. It is not possible to study systematically the effect of solvent conditions, e.g. added salt concentration, on biopolymer properties by means of simulations alone. In the last part of the paper we review a more analytical approach we have developed to study polyelectrolyte properties of solvated biopolymers. The results are compared with computer simulations. 

Vibrational spectroscopy has played a very important role in the development of potential functions for molecular mechanics studies of proteins. Force constants which appear in the energy expressions are heavily parameterized from infrared and Raman studies of small model compounds. One approach to the interpretation of vibrational spectra for biopolymers has been a harmonic analysis whereby spectra are fit by geometry and/or force constant changes. There are a number of reasons for developing other approaches. The consistent force field (CFF) type potentials used in computer simulations are meant to model the motions of the atoms over a large ranee of conformations and, implicitly temperatures, without reparameterization. It is also desirable to develop a formalism for interpreting vibrational spectra which takes into account the variation in the conformations of the chromophore and surroundings which occur due to thermal motions. 

Patapoff, T. W., Mrsny, R. J., and Lee, W. A., The application of size exclusion chromatography and computer simulation to study the thermodynamic and kinetic parameters for short-lived dissociable protein aggregates, Anal. Bio-chem., 212, 71, 1993. 

Derrick studied the interaction of L-tryptophan and ibuprofen with human serum albumin (HSA),74 which is an abundant transport blood protein capable of binding efficiently several species.75 They acquired 1H NMR spectra of L-Tryptophan-HSA system for different ligand protein molar ratios, that is 3 1, 5 1, 7 1 and 10 1. The aromatic resonances of L-Tryptophan are difficult to be observed due to the overlap with HSA signals, even at 10 1 molar ratio, so that the spectral subtraction was performed. D values of L-Tryptophan were calculated by integration of the subtracted spectra and were in good agreement with those predicted by computer simulations. In the case of ibuprofen, only for 140 1 molar ratio, the resonances of ibuprofen are clearly visible also in this case, the... 

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