We performed structure calculations for the V3 loop of the HIV-1 envelope glycoprotein gp120. Experimental restraints derived from liquid- and solid-state NMR data were used, and different simulated annealing protocols were evaluated using the CHARMM program. One paper has been published and another manuscript will soon be submitted for publication. We concluded our study of peptide binding to cyclin- dependent kinase 5. Mutagenesis experiments and molecular modeling were used to identify the substrate binding site. The results were published. We continued to develop Monte Carlo simulation techniques in the CHARMM program, incorporating biased searching of main-chain and side-chain dihedral conformations. The methods were tested with preliminary folding simulations of an alpha helix using a Generalized Born treatment of the solvation free energy. We made a homology model of dihydrofolate reductase (DHFR) from Streptococcus pneumonia from the crystal structure of DHFR from E. coli. Monte Carlo simulations were performed on the homology model with the antibiotic trimethoprim bound. The structural effects of mutating Ile 100 to Leu or Met were investigated. Simulations suggested that the mutation Ile100Leu results in main-chain relaxation that breaks a hydrogen bond between residue 100 and trimethoprim and thus confers resistance to trimethoprim. A manuscript is in preparation.We made a homology model of the extracellular domain of the human calcium receptor (hCaR ECD) based on the crystal structure of E. coli leucine/isoleucine/valine periplasmic binding protein. Experimental data and the model were used to infer the putative dimer interface of hCaR ECD. A paper has been published. - molecular modeling, structure-function relationship, computer simulation
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