Computer aided drug design methods & quantitative structure-activity/property relationships

Suman Sirimulla, University of Texas at El Paso


The first part of dissertation consists of development of a QSAR model for 229 mutagenic aromatic amines and a QSPR model of partial molar volumes of amino acids. A common procedure for QSAR analysis consist of data selection (generally sets of homologous series of compounds and their corresponding biological activities), tabulation of trial physicochemical or molecular structural descriptors, followed by a multilinear statistical analysis to derive a statistically valid QSAR correlation of the activity data making use of a subset of the trial descriptors. A final important step is cross-validation to assess the putative predictive (rather than just correlative) capabilities of the derived QSAR model equation. The results of a very successful elementary QSA(/P)R studies using substituent indicator variables, coupled with calculated theoretical parameters for the compounds in the work outlined above are presented.^ The second part of the dissertation illustrates that betalactoglobulin and human serum albumin can be used as a vehicle to improve the bioavailability of curcumin and it’s derivatives. Curcumin a major component of Indian spice turmeric (Curcuma longa), possesses diverse anti-inflammatory, antitumour and antioxidant properties. Several studies have confirmed that curcumin can reduce the oxidative/nitrosative stress and there by decrease the neuronal attrition. But the bioavailability of curcumin is poor and has raised several concerns regarding limited clinical impact. The aim of this study was to find molecules similar to curcumin which can assist in decreasing nitrosative stress and possess enhanced bioavailability. Here, we examined the use of beta-lactoglobulin as a vehicle to transport molecules to the gut. Curcumin analogs were searched from Zinc database and 6457 compounds were selected for the study. These compounds were docked to betalactoglobulin using Glide to find the best fit ligands. Our findings indicated four compounds that have better binding to betalactoglobulin and efficient NOx (free radical) scavenging activity.^

Subject Area

Chemistry, Biochemistry|Chemistry, Pharmaceutical

Recommended Citation

Sirimulla, Suman, "Computer aided drug design methods & quantitative structure-activity/property relationships" (2010). ETD Collection for University of Texas, El Paso. AAI3409177.