Combinatorial Chemistry & High Throughput Screening - Volume 4, Issue 8, 2001

The complexation of p-tert-butylphenyl p-tert-butylbenzoate, N- (p-tert-butylphenyl)-p-tert-butylbenzamide and a bisadamantyl-phosphate derivative with a beta-cyclodextrin derivative formed by two cyclodextrin units linked by a disulfide bridge on one of the C6 atoms have been studied by computational methods (free energy perturbation (FEP) and Molecular Mechanics / Poisson Bolzmann Surface Area (MM / PBS Read More

An overview of the simplified linear interaction energy (LIE) method for calculation of ligand binding free energies is given. This method is based on force field estimations of the receptor-ligand interactions and thermal conformational sampling. A notable feature is that the binding energetics can be predicted by considering only the intermolecular interactions between the ligand and receptor. The approximations behind this appro Read More

The complexes of human neutrophil elastase with a series of 40 N3-substituted trifluoromethylketone-based pyridone inhibitors have been modelled. The series spans three orders of magnitude in inhibition constants despite the fact that it was originally developed in an attempt to improve the oral activity of a lead compound. Ligand-receptor interaction energies calculated using molecular mechanics did not correl Read More

This review describes computational procedures for deriving the amino acid sequences that are compatible with a given protein backbone structure. Such procedures can be used to gain insight into the constraints imposed by the 3D structure of the protein sequence, or to design proteins that are likely to adopt a given backbone conformation. We start by presenting a short overview of the various types of approac Read More

A new computational approach (PEP) is presented for the structure-based design of linear polymeric ligands consisting of any type of amino acid. Ligands are grown from a seed by iteratively adding amino acids to the growing construct. The search in chemical space is performed by a build-up approach which employs all of the residues of a user-defined library. At every growing step, a genetic algorithm is used for conformation Read More

The genetic information that determines the structure and function of living organisms is encoded in the nucleotide sequence of double-stranded DNA molecules. Despite an apparent structural homogeneity displayed by DNA, subtle local variations in structure and dynamics are functionally significant. Short sequences exhibit specificity for regulatory and catalytic proteins, which mediate fundamental processes necessary to Read More

We have recently developed a theoretical means of studying the mechanical and interaction properties of nucleic acids as a function of their base sequence. This approach, termed ADAPT, can be used to obtain the physical properties of millions of base sequences with only modest computational expense. ADAPT is based on a multi-copy algorithm using special nucleotides (“lexides”) containing all four standard base Read More

Recent tools that analyze microarray expression data have exploited correlation-based approaches such as clustering analysis. We describe a new method for assessing the importance of genes for sample classification based on expression data. Our approach combines a genetic algorithm (GA) and the k-nearest neighbor (KNN) method to identify genes that jointly can discriminate between two types of samples (e.g. normal Read More