QSAR STUDIES ON HUMAN CARBONIC ANHYDRASE II INHIBITORS

Carbonic anhydrase II is one of the forms of human α carbonic anhydrases which are ubiquitous metalloenzymes that catalyze inter-conversion of carbon dioxide and water to bicarbonate and proton, overexpression of which leads to disorders such as glaucoma. 2D and 3D Quantitative Structure Activity Relationship studies were carried out on previously synthesized series of sulfanilamide derivatives by VLife MDS software using stepwise variable, multi-linear regression and k-nearest neighbor molecular field analysis methods. 2D-QSAR model depicts contribution of halogens (such as chlorine and fluorine), methylene and oxygen atoms to inhibition of human carbonic anhydrases II activity. Using k-nearest neighbor molecular field analysis method two 3D-QSAR models (model A and B) were generated from which model A was found to be the best validated model with q2 (0.9494), pred_r2 (0.7367) and q2 _ se (0.2037). It displayed the fact that the inhibitory action of sulfanilamide derivatives against human carbonic anhydrases II is influenced by hydrophobicity and electro positivity.

Prediction of HIV drug resistance based on the 3D protein structure: Proposal of molecular field mapping

A method for predicting HIV drug resistance by using genotypes would greatly assist in selecting appropriate combinations of antiviral drugs. Models reported previously have had two major problems: lack of information on the 3D protein structure and processing of incomplete sequencing data in the modeling procedure. We propose obtaining the 3D structural information of viral proteins by using homology modeling and molecular field mapping, instead of just their primary amino acid sequences. The molecular field potential parameters reflect the physicochemical characteristics associated with the 3D structure of the proteins. We also introduce the Bayesian conditional mutual information theory to estimate the probabilities of occurrence of all possible protein candidates from an incomplete sequencing sample. This approach allows for the effective use of uncertain information for the modeling process. We applied these data analysis techniques to the HIV-1 protease inhibitor dataset and developed drug resistance prediction models with reasonable performance.

Strain-induced modulation of temperature characteristics in ferrimagnetic Tb–Fe films

This study investigates the effect of strain on the compensation temperature of ferrimagnetic Tb–Fe films formed on a flexible substrate. The compensation temperature is determined by the anomalous Hall measurement, and an application of 1.2% tensile strain reduces the compensation temperature by 12 K. X-ray magnetic circular dichroism reveals that approximately 5% of Fe magnetic moment and approximately 1% of Tb magnetic moment are reduced by an application of 0.9% tensile strain at the room temperature. To understand the greater reduction in Fe magnetization compared with that in Tb and the compensation temperature reduction simultaneously, a model applying molecular field theory is analyzed. Changes in three types of exchange coupling between Fe and Tb atoms are speculated to be caused by the strain.