Model building molecular dynamics

MI Sutcliffe, CM Dobson, RE Oswald. Solution structure of neuronal bungarotoxm determined by two-dimensional NMR spectroscopy Calculation of tertiary structure using systematic homologous model building, dynamical simulated annealing, and restrained molecular dynamics. Biochemistry 31 2962-2970, 1992. 

The authors thank Rik Moereels (Janssen Research Foundation, Beerse, Belgium) for his direction during the de novo model building stage of the project and Harold Almond, Jr., for helpful discussions. We also thank Marco Ceruso for his advice and analysis of the final receptor model in particular, he examined phi-psi space for angle violations and relaxed the relevant regions through molecular dynamics simulations. 

In addition, one of the most relevant interactions resulting from the molecular dynamics calculations was found to be an aromatic contact between the 2,5-dichlorophenyl substituent and a Phe residue of the a -AR model. It is described in our pharmacophore as a more generic hydrophobic interaction involving the substituted phenyl ring attached to the piperazine nucleus. All these considerations prompted us to retrace the steps performed to build the pharmacophore model for a -AR inhibitors and check for any possibility of improving it. 

Use the SWISS-MODEL (9) to build possible protein structures for these genes dock potential broad-spectrum antibiotics candidates to the active sites with AutoDock (10) and use molecular dynamics simulations to research possible binding modes between antibiotics and target proteins (11). 

Nevertheless, ab initio or semiempirical quantum chemical calculations, with clusters to represent the catalytic solid material, can help build up a model of the catalytic system and study effects of modifications [52], Even simulation of the molecular dynamics of the interaction between reactants or intermediates, together with replication of the unit cell of the catalytic solid in a simple force field, may describe observed effects in a catalytic system and may be able to predict the effect of catalyst modifications [53]. 

Tel. 800-424-9737, fax 415-491-8311 (U.S.A.), tel. 41-38-337633 (U.K.) Model building, display, charge density, electrostatic potential, and molecular orbital plots. Stick, sphere, and dot surface display. 2D to 3D conversion. Protein and DNA fragment libraries. MM+, BIO+ (implementations of MM2 and CHARMM, respectively), OPLS, and AMBER molecular mechanics and dynamics. Solvent box. Semiempirical calculations by Extended Hiickel, CNDO, INDO, MINDO/3, MNDO, AMI, and PM3. Originated at Hypercube, Inc. (Dr. N. Ostlund et al.), of Ontario, Canada. Runs under Windows on a 386 or 486 PC and under Motif on a Silicon Graphics workstation. 

Tel. 415-476-4637, fax 415-476-0688, e-mail pak cgl.ucsf.edu Assisted Model Building using Energy Refinement. Energy minimization, molecular dynamics, and free energy perturbation (FEP) calculations. SPASMS (San Francisco Package of Applications for the Simulation of Molecular Systems). VAX, Cray versions. 

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