Molecular modeling protocols

Combining 2D-NOESY and 2D-ROESY NMR experiments with molecular modelling protocols, Kuhn and Kunz32 have been able to study the saccharide-induced peptide conformational behaviour of the recognition region of Ll-Cadherin. The detailed conformational analysis of this key biomolecule not only proves that the saccharide side chain exerts a marked influence on the conformation of the peptide chain, but also that the size and type of the saccharide indeed strongly affects the conformation of the main chain. 

We thus set out to examine the role of pro-hormone conformation in its own maturation by solving the solution phase conformation of pro- (and pre-pro) GnRH protein through the use of NMR and molecular modeling protocols. 

Cerqueira, N.M. Fernandes, P.A. Eriksson, L.A. Ramos, M. J. MADAMM AMultistaged Docking with an Automated Molecular Modeling Protocol. Proteins Struct Funct Bio-inf 2009, 74 (1), 192-206. 

The computational requirements of these calculations are relatively modest on modern computers. However, some groups have exploited computer power to design ambitious molecular replacement protocols in which many models are assessed in parallel (see Section 12.6). 

Chart 8 Chemical structures of the CA4 boronic acid bioisostere (9) and of MDL-27048. The former was proposed by a structure-based molecular modeling study, the latter was used to elaborate a virtual screening protocol for the identification of novel chalcone CSI... 

At present, many popular applied molecular evolution protocols do not involve mutation or recombination. The laboratory technique-based models presented in this section are of this type. Incorporating mutation requires fitness landscape models or some other means of relating molecular properties to particular sequences. The more abstract models reviewed later allow for mutation and recombination and are based heavily on landscape structure. The models in the present section are based on affinity distribution p(Ka), the probability that a ligand chosen at random from the library has affinity Ka. 

Besides those listed here, there are other molecular modeling programs developed in academic and industrial laboratories around the world however, because the availability, documentation, and degree of support of these other programs are highly variable, it is impractical to include them all. More and more frequently, workstation software is being transferred between computational chemists via file transfer protocol (ftp) or electronic mail over Internet, Bitnet, and similar networks of computers. In these situations, the cost is nothing, but reliability of the software can be unknown. 

---