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V M Kulkarni

Publications and source records attributed to V M Kulkarni.

27 records · Page 2Linked to original sources
PubMedDate not supplied

A molecular dynamics study of the three-dimensional model of human synovial fluid phospholipase A2--transition state mimic complexes.

Different modes of binding of transition state mimics: amide, phosphonate and difluoro ketone, to human synovial fluid phospholipase A2 (HSF PLA2) are studies by molecular dynamics simulations computed in solvent. The results are analysed in the light of primary binding sites. Hydrogen bonding interaction plays an important role for amino acids such as Gly32, Val30, and Glu55, apart from the well known active site residues viz Asp48, Gly25, Gly29, Gly31, His27, His47, Lys62, Phe23, Asn114 and Tyr112. In addition, the hydrogen bonding interaction between Sn-1 tetrahedral phosphonate group of amide and difluoro ketone inhibitors and crystallographic water molecules (H2O 523, H2O 524 and H2O 401) seems to have a significant role. Many of the active site charged residues display considerable movement upon ligand binding. The structural effects of ligand binding were analyzed from RMS deviations of C alpha in the resulting energy-minimized average structures of the receptor-ligand complexes. The values of the RMS deviations differ among the HSF PLA2s, in a pattern that is not the same for the three complexes. This suggests that ligands with different pharmacological efficacies induce different types of conformational changes of the receptor. Our active-orientation model is, at least qualitatively, consistent with experimental data and should be useful for the rational design of more potent inhibitors.

Amides↗
PubMedDate not supplied

Eigen value analysis of HIV-1 integrase inhibitors.

A three-dimensional quantitative structure activity relationship using the eigen value analysis (EVA) paradigm applied to 41 HIV-1 integrase inhibitors that inhibit integrase mediated cleavage (3'-processing step) and integration (3'-strand transfer step) in vitro was performed. The training set consisted of 35 molecules from five structurally diverse classes: salicylhydrazines, lichen acids, coumarins, quinones, and thiazolothiazepines. Models derived using semiempirical (MOPAC AM1 and PM3) calculated normal-mode frequencies were compared. The predictive ability of each resultant model was evaluated using a test set comprised of six molecules belonging to a different structural class: hydrazides. Models derived using AM1 method showed considerable internal as well as external predictivity (r(2)(cv) = 0.806, r(2)(pred) = 0.761 for 3'-processing and r(2)(cv) = 0.677, r(2)(pred) = 0.591 for 3'-strand transfer).

HIV Integrase↗
PubMedDate not supplied

Three-dimensional quantitative structure-activity relationship (QSAR) and receptor mapping of cytochrome P-450(14 alpha DM) inhibiting azole antifungal agents.

Molecular modeling was performed by a combined use of conformational analysis and 3D-QSAR methods to distinguish structural attributes common to a series of azole antifungal agents. Apex-3D program was used to recognize the common biophoric structural patterns of 13 diverse sets of azole antifungal compounds demonstrating different magnitudes of biological activity. Apex-3D identified three common biophoric features significant for activity: N1 atom of azole ring, the aromatic ring centroid 1, and aromatic ring centroid 2. A common biophore model proposed from the Apex-3D analysis can be useful for the design of novel cytochrome P-450(14 alpha DM) inhibiting antifungal agents.

Antifungal Agents↗
PubMedDate not supplied

Structure based prediction of binding affinity of human immunodeficiency virus-1 protease inhibitors.

A series of computations were performed to derive a strategy for the prediction of binding affinities of non-peptidic human immunodeficiency virus-1 (HIV-1) protease inhibitors. This paper describes the development of a 3D quantitative structure-activity relationship (3D-QSAR) methodology by using receptor information of HIV-1 protease. The docking and molecular dynamics simulations were performed on a model ligand/enzyme complex to optimize the variables involved in the generation of ligand/enzyme models. The protonation scheme of the active site aspartic acid residues of HIV-1 protease was derived from a computational study. The active site aspartate is monoprotonated with a proton placed on the OD1 atom of the ASP B25. This protocol of docking and molecular dynamics (MD) simulation was then used to derive the ligand-enzyme complexes of the molecules used in the present study. The molecular mechanics interaction descriptors were calculated from these ligand/enzyme models. A partial least squares (PLS) method was used to derive a linear correlation between the interaction descriptors and the biological activity. A good correlation was observed when the change in the energy of the ligand upon complex formation and the electrostatic contributions to the solvation energy of the ligand were included in the QSAR analysis. A highest cross-validated q2 value of 0.649 was observed. This model had a conventional r2 of 0.725, and when this model was used to predict the activity of the external test set, it produced a r2pred of 0.761. The total interaction energy was partitioned into interactions in different subsites and interactions with each of the amino acid residues of the enzyme. The PLS analysis using these descriptors helped to identify the important interactions which can be exploited for the design of HIV-1 protease inhibitors.

HIV Protease↗
PubMedDate not supplied

Use of adrenal vein conduit for splenorenal shunts: a case report.

We report a case with extrahepatic portal venous obstruction (EHPVO), who presented with recurrent bleeding following a previous devascularization procedure and needed an emergency distal spleno-renal shunt (DSRS). Due to technical difficulty because of previous scarring, the adrenal vein was used as a conduit between the splenic vein and renal vein. The shunt's patent and the patient has been bleed-free for 2 years.

Adolescent↗
PubMedDate not supplied

Ruptured true aneurysm of the splenic artery: an unusual cause of haemoperitoneum.

True aneurysm of the splenic artery is rare. Two cases of ruptured true splenic artery aneurysms are presented. The first patient was a 62-year-old female who presented within 6 hours of the onset of symptoms. The other was a 27-year-old non-alcoholic male patient who was admitted in a state of shock after 2 days of observation in a peripheral hospital. Both patients had haemoperitoneum and were subjected to exploratory laparotomy. Aneurysmectomy was performed in both the patients in addition to left splenopancreatectomy in the first case and splenectomy in the second. However, due to the prolonged preoperative shock, the second patient succumbed on the third postoperative day.

Abdomen, Acute↗
PubMedDate not supplied

Gastric lipoma presenting as obstruction and hematemesis.

A rare case of gastric lipoma presented to us with hematemesis and symptoms of obstruction. On oesophagoduodenoscopy, a mass projecting in the lumen of stomach was found. Barium meal examination revealed a mass in the antral region suggestive of malignancy. The diagnosis of lipoma was suspected only after exploration. It was confirmed following incision through the serosa. The lipoma was enucleated without any damage to mucosa.

Aged↗