A5102899448- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Mass Spectrometry Techniques and Applications
- Phenothiazines and Benzothiazines Synthesis and Activities
- Plant biochemistry and biosynthesis
- Crystallization and Solubility Studies
- Free Radicals and Antioxidants
- Synthesis of Organic Compounds
- X-ray Diffraction in Crystallography
- Synthesis and biological activity
- Microbial Natural Products and Biosynthesis
- Advanced Combustion Engine Technologies
- Carbohydrate Chemistry and Synthesis
- Synthesis and Biological Evaluation
- Plant Molecular Biology Research
- Biochemical and Molecular Research
- Research on Leishmaniasis Studies
- Crystal structures of chemical compounds
- Phosphodiesterase function and regulation
- Spectroscopy Techniques in Biomedical and Chemical Research
- Analytical Chemistry and Chromatography
- Biodiesel Production and Applications
- Lubricants and Their Additives
- Plant Reproductive Biology
- Enzyme Structure and Function
Schrodinger (United States)
2018-2023
University of California, San Diego
2011-2014
Howard Hughes Medical Institute
2011-2014
Center for Theoretical Biological Physics
2011
Universidade Federal de Juiz de Fora
2010
Universidade Federal Fluminense
2006-2008
Accurate prediction of ligand binding affinities is key importance in small molecule lead optimization and a central task computational medicinal chemistry. Over the years, advances both computer hardware methodologies have established free energy perturbation (FEP) methods as among most reliable rigorous approaches to compute protein–ligand energies. However, accurate description ionization tautomerism ligands still major challenge structure-based affinities. Druglike molecules are often...
Cyclic nucleotide phosphodiesterases (PDE's) are metalloenzymes that play a key role in regulating the levels of ubiquitous second messengers, cyclic adenosine monophosphate (cAMP) and guanosine (cGMP). In humans, 11 PDE protein families mediate numerous biochemical pathways throughout body effective drug targets for treatment diseases ranging from central nervous system disorders to heart pulmonary diseases. PDE's also share highly conserved catalytic site (about 50%), thus making design...
Undecaprenyl pyrophosphate synthase is a cis ‐prenyltransferase enzyme, which required for cell wall biosynthesis in bacteria. an attractive target antimicrobial therapy. We performed long molecular dynamics simulations and docking studies on undecaprenyl to investigate its dynamic behavior the influence of protein flexibility design inhibitors. also describe first X‐ray crystallographic structure Escherichia coli apo ‐undecaprenyl synthase. The indicate that highly flexible protein, with...
Significant improvements have been made in the past decade to methods that rapidly and accurately predict binding affinity through free energy perturbation (FEP) calculations. This has driven by recent advances small-molecule force fields sampling algorithms combined with availability of low-cost parallel computing. Predictive accuracies ∼1 kcal mol-1 regularly achieved, which are sufficient drive potency optimization modern drug discovery campaigns. Despite robustness these FEP approaches...
Recently 1-hydroxyacridone derivatives were described as a new class of non-nucleoside inhibitors Herpes Simplex Virus-1 (HSV-1), the agent most common human diseases.Based on these molecules, we applied rigid analogue and isosteric replacement approaches to design synthesize five benzo[b]thieno[3,2-h]-1,6-naphthyridines 8a-e feasible anti-HSV prototypes.Herein synthesis this series compounds theoretical evaluation drug score likeness by using an in silico ADMET screening.
With the rise in antibiotic resistance, there is interest discovering new drugs active against targets. Here, we investigate dynamic structures of three isoprenoid synthases from Mycobacterium tuberculosis using molecular dynamics (MD) methods with a view to drug leads. Two enzymes, cis-farnesyl diphosphate synthase (cis-FPPS) and cis-decaprenyl (cis-DPPS), are involved bacterial cell wall biosynthesis, while third, tuberculosinyl adenosine (Rv3378c), virulence factor formation. The MD...
We describe a mild and efficient method for the formation of 3-(2'-aminoaryl)pyrazoles in excellent yields from reactions 4-chloroquinolines with hydrazine. These heterocyclic ring opening occur under much milder conditions then previously described.
The title compound, C 17 H 14 BrNO 5 , was studied as part of a study on the biological properties pyranoquinoline derivatives. Alkylation parent shown to have occurred at carbonyl rather than amino site. molecules are linked by C—H...O hydrogen bond forming (5) chains along [001].
Significant improvements have been made in the past decade to methods that rapidly and accurately predict binding affinity through free energy perturbation (FEP) calculations. This has driven by recent advances small molecule force fields sampling algorithms combined with availability of low-cost parallel computing. Predictive accuracies ~1 kcal mol-1 regularly achieved, which are sufficient drive potency optimization modern drug discovery campaigns. Despite robustness these FEP approaches...
First Page
The title compound, C 17 H 14 ClNO 5 has been shown to be isostructural with the bromo analogue, confirming site of alkylation within structure and pyranoquinoline ring system. As molecules are linked by a C—H...O hydrogen bond forming (5) chains along [001].