Many of the structures in PubChem are annotated with activities determined in high-throughput screening (HTS) assays. Because of the nature of these assays, the activity data are typically strongly imbalanced, with a small number of active compounds contrasting with a very large number of inactive compounds. We have used several such imbalanced PubChem HTS assays to test and develop strategies ...

Motivation: Technological advances have enabled the identification of an increasingly large spectrum of single nucleotide variants within the human genome, many of which may be associated with monogenic disease or complex traits. Here, we propose an integrative approach, named FATHMM-MKL, to predict the functional consequences of both coding and non-coding sequence variants. Our method utilizes...

Identifying the small number of rare causal variants contributing to disease has been a major focus of investigation in recent years, but represents a formidable statistical challenge due to the rare frequencies with which these variants are observed. In this commentary we draw attention to a formal statistical framework, namely hierarchical modeling, to combine functional genomic annotations w...

Continuous dopaminergic delivery is recognized for the capacity to ameliorate symptoms in Parkinson's disease (PD). In advanced PD the short comings of orally administered Levodopa/Carbidopa include fluctuations resulting in unstable effect and dyskinesia. Levodopa/Carbidopa intestinal gel, LCIG, (Duodopa®, Abbott Laboratories) is delivered continuously through a percutaneous endoscopic gastros...

Schiff base, azetidinone and 4-thiazolidinone derivatives of para aminosalicylic acid were synthesised. It was planned to employ the structure based computer aided drug designing (CADD) to Schiff base, azetidinone and 4thiazolidinoneof para aminosalicylic acid. Approach was employed to understand the probable binding of para aminosalicylic acid on the active site of AMpC enzyme of HKY28 which w...

HCV (Hepatitis C virus) that causes chronic liver disease. HCV NS5B RNA-dependent RNA polymerase (RbRp) and NS3 protease are able to affect virtual replication of genes. Computer-aided drug design (CADD) aims at designing new molecules with pharmacological activity. In this study, we used the Discovery Studio 2.0 program and the scoring function to estimate the Dock Score, piecewise linear pote...

We describe an algorithm based on motion-planning techniques to determine the existence of an accessible route through a facility for a wheeled mobility device. The algorithm is based on LaValle's work on Rapidly-exploring Random Trees (RRT) and is enhanced to take into consideration the particularities of the accessible route domain. Specifically, the algorithm is designed to allow performance...

In Computer-Aided-Drug-Design (CADD), the electrostatic interactions contribute strongly to the interaction between the drug-molecule and the target. Further, the Coulomb term is crucial for calculating the electrostatic contribution to the solvation energy. In spite of this, conventional Force Fields use the obsolete physical concept of point-monopoles (net atomic charges) and thus, are not ab...