Molecular modeling protein structure prediction

In general the relevance of predictions of structure-function relationships based on molecular modeling and structural bioinformatics are threefold. First they can be used to answer the question of which partners (proteins) could interact. Second, predictions generate new hypotheses about binding site, about molecular mechanisms of activation and interaction between two partners, and can lead to new ideas for pharmacological intervention. The third aim is to use the predictions for structure-based drug design. 

Peitsch, M. C., Schwede, T., Diemand, A., and Guex, N. (2002) Protein structure prediction by comparison homology-based modeling. Current Topics in Computational Molecular Biology, 449-466. 

The REFINER model had been tested in the CASP5 (every second year community-wide Critical Assessment of Techniques for Protein Structure Prediction) experiment and in a benchmark of de novo prediction of protein fragments. Both tests have shown better performance than that achieved by standard molecular modeling tools. During the next round, CASP6 of the protein structure prediction, the REFINER model produced several very good predictions, especially in the new fold category. 

A wide variety of energy functions have been used as part of the various GA-based protein structure prediction protocols. These range from the hydrophobic potential in the simple HP lattice model [19] to energy models such as CHARMM, based on full fledged, detailed molecular mechanics [9]. Apparently, the ease by which various energy functions can be incorporated within the framework of GAs as fitness functions encouraged researchers to modify the energy function in very creative ways to include terms that are not used with the traditional methods for protein structure prediction. 

Buchwald P and Bodor N. Octanol-water Partition of Nonzwitterionic Peptides Predictive Power of a Molecular Size-based Model. Proteins Structure, Function and Genetics 1998 30 86-99. 

There is a considerable impetus to predict accurately protein structures from sequence information because of the protein sequence/structure deficit as a consequence of the genome and full-length cDNA sequencing projects. The molecular mechanical (MM) approach to modeling of protein structures has been discussed in section 9.2, and the protein secondary structure prediction from sequence by statistical methods has been treated in section 9.5. The prediction of protein structure using bioinformatic resources will be described in this subsection. The approaches to protein structure predictions from amino acid sequences (Tsigelny, 2002 Webster, 2000) include ... 

Keywords Multiscale modeling, Nanotube growth, Non-adiabatic molecular dynamics, Organometallic structures. Protein structure prediction. Reactive molecular dynamics... 

Computer Graphics and Molecular Modeling Conformational Analysis 1 Electrostatic Catalysis Molecular Docking and Structure-based Design Protein Structure Prediction in ID, 2D, and 3D Structural Chemistry Application of Mathematics Symmetry and Chirality Continuous Measures Symmetry in Chemistry. 

A. Neumaier, Molecular modeling of proteins and mathematical prediction of protein structure, SIAM Rev. 39 (1997), 407-460. 

Moreover, molecular modeling is one key method of a wide range of computer-assisted methods to analyze and predict relationships between protein sequence, 3D-molecular structure, and biological function (sequence-structure-function relationships). In molecular pharmacology these methods focus predominantly on analysis of interactions between different proteins, and between ligands (hormones, drugs) and proteins as well gaining information at the amino acid and even to atomic level. 

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