Molecular modelling-computational approach of drug designing

The molecular modelling is the general term used to describe the use of computer to construct the molecule and perform a variety of calculation on there molecule in order to predict their chemical characteristics and behavior.rational drug design is also introduce with the help of artificial intelligence.the protein folding problem entails the mathematical prediction of tertiary,3-dimensional protein structure given that the primary linear structure is defined by the sequence of coine acids of the protein.it is one of the most challenging problems in current biochemistry,and is a very rich source of interesting problems in mathematical modeling and numerical analysis,requiring an interplay of techniques in digen value calculations,stiff differential equations,stochastic differential equations,local and global optimization,nonlinear least squares.even topologibal concepts like the morse index and invariants in knot theory have been used.an extensive recent report from the US national research council on the mathematical challenges from theoretical and computational chemistry shows the protein folding problem embedded into a large variety of other mathematical challenges in chemistry.imatinib-acquired resistance related to the presence of secondary point mutations has become a frequent event in gastrointestinal stromal tumors.here transient transfection experiments with plasmies carrying two different KIT-acquired point mutations were performed clog with immunoprecipitation of total protein extracts,derived from imatinib-treated and untreated cells.the molecular mechanics/poisson boltzmann surface area computational techniques were applied to study the interactions of the wild type and mutated receptors with imatinib at the molecular level.biochemical analyses showed KIT phosphorylation in bell transfected with vectors carrying the specific mutant genes.imatinib treatment demonstrated that T670I was insensitive to the drug at all the applied concentrations,whereas V654A was inhibited by 6micro meter of imatinib.the modeling of the mutated receptors revealed that both substitutins affect imatinib-binding sites,but u2 a different extent:T670I substantially modifies the binding pocket,whereas V654A induces only relatively confined structural changes.