CHARMm Chemical

CHARMm Chemical information Chemical information courses Chemical structure indexing... 

California), Sibyl (Tripos, Missouri), ChemX (Chemical Design, UK), BioGraf (Molecular Simulations, California), Charmm/Quanta (Polygen Corp., Massachusetts), PC Model (Serena Software, Indiana), ChemLab (ChemLab Inc., Illinois), and a large number of personal computer-based packages. 

The chemical reaction catalyzed by triosephosphate isomerase (TIM) was the first application of the QM-MM method in CHARMM to the smdy of enzyme catalysis [26]. The study calculated an energy pathway for the reaction in the enzyme and decomposed the energetics into specific contributions from each of the residues of the enzyme. TIM catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP) as part of the glycolytic pathway. Extensive experimental studies have been performed on TIM, and it has been proposed that Glu-165 acts as a base for deprotonation of DHAP and that His-95 acts as an acid to protonate the carbonyl oxygen of DHAP, forming an enediolate (see Fig. 3) [58]. 

Figure 16.12 Chemical structure (a), and CHARMm molecular modeling picture (b), of the dendritic box [159]...

Hobza P, Kabelac M, Sponer J, Mejzlik P, Vondrasek J (1997) Performance of empirical potentials (AMBER, CFF95, CVFF, CHARMM, OPS, POLTEV), semiemprical quantum chemical methods (AMI, MNDO/M, PM3) and ab initio Hartree-Fock method for interaction of DNA bases comparison of nonempirical beyond Hartree-Fock results, J Comp Chem, 18 1136-1150... 

PCMODEL are supported by developers at Columbia University and Indiana University, respectively. Neither is backed by a large marketing or sales force. Yet each has enjoyed noteworthy success in terms of being used in publications. Also plotted are CJACS hits of Chemical Design Ltd., which supports Chem-X, and Serena Software, which has PCMODEL. Literature mention of the Chem-X package exceeded that of Insight/Discover, SYBYL, and Quanta/CHARMm for at least one year in the 1980s, but publications from users of Chem-X have not kept up and have fluctuated around the same level in the last few years. 

Nonbonded interactions consist of van der Waals (VDW) and electrostatic potentials. Examples of the valence force field approach include UFF or DREIDING [54], MM2/MMP2 [55], AMBER [56], and CHARMM [57]. The parameters of the potentials can be determined from either experiments or ab initio quantum chemical methods [58]. 

Standard molecular mechanics (MM) methods (e.g. the popular force fields developed for AMBER, CHARMM and GROMOS decribed in Section 2 above) provide a good description of protein structure and dynamics, but cannot be used to model chemical reactions. This limitation is due their simple functional forms (e.g. harmonic terms for bond stretching) and inability to model changes in electronic polarization (because of the invariant point partial atomic charge used by these molecular mechanics methods to represent electrostatic interactions). 

In this paper we develop a new method for finding the three-dimensional space that surrounds a substrate/ligand. This space, which is the chemical equivalent of the receptor, is represented as a protein structure, referred herein as a "pseudo-receptor". A variety of computational tools are used to create the pseudo-receptor. A molecular mechanics and dynamics program, CHARMm(l), is used to calculate the energy and conformational features of the pseudo-receptor. The program QUANTA(l) is used to define the preliminary protein sequence, secondary structure, graphically examine molecular interactions, interface with CHARMm, and model amino-acid mutations in the protein sequence. 

This simple representation is used in, e.g., the CVFF and CHARMm force fields. As for bonds, two parameters are needed, a reference angle and a force constant, and only a fraction of all the possible combinations of atom types are represented in real chemical structures. In certain cases, generalized parameters are used because of lack... 

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