Abstract
Free energy perturbation studies have been performed on Glucoamylase II (471) from Aspergillus awamori var. X100 complexed with three different inhibitors: (+)lentiginosine, (+)(1S,2S,7R,8aS) 1,2,7-trihydroxyindolizidine, (+)(1S,2S,7S,8aS) 1,2,7-trihydroxyindolizidine and the inactive compound (+)(1S,7R,8aS)-1,7-dihydroxyindolizidine. Molecular dynamic simulations were carried out using a recently developed procedure for fast Free Energy Perturbation calculations. In this procedure only a sphere of 1.8 nm around the central atom of the inhibitor is considered in the calculations. Crystallographic restraints are applied over this reduced system using a generated electron density map. The obtained values for the free energy differences agree with experimental data showing the importance of fast calculations in drug design even when the crystallographic structure of the complex is not available. As the method uses only the crystallographic structure of the receptor, it is possible to test the possible efficiency of even still not synthesised ligands, making the pre-selection of compounds much easy and faster.
Keywords: glycosidase inhibitors, free energy calculation, glycosidase complexes
Medicinal Chemistry
Title: Free Energy Perturbation Calculations on Glucosidase-Inhibitor Complexes
Volume: 1 Issue: 5
Author(s): F. M. Ruiz and J. R. Grigera
Affiliation:
Keywords: glycosidase inhibitors, free energy calculation, glycosidase complexes
Abstract: Free energy perturbation studies have been performed on Glucoamylase II (471) from Aspergillus awamori var. X100 complexed with three different inhibitors: (+)lentiginosine, (+)(1S,2S,7R,8aS) 1,2,7-trihydroxyindolizidine, (+)(1S,2S,7S,8aS) 1,2,7-trihydroxyindolizidine and the inactive compound (+)(1S,7R,8aS)-1,7-dihydroxyindolizidine. Molecular dynamic simulations were carried out using a recently developed procedure for fast Free Energy Perturbation calculations. In this procedure only a sphere of 1.8 nm around the central atom of the inhibitor is considered in the calculations. Crystallographic restraints are applied over this reduced system using a generated electron density map. The obtained values for the free energy differences agree with experimental data showing the importance of fast calculations in drug design even when the crystallographic structure of the complex is not available. As the method uses only the crystallographic structure of the receptor, it is possible to test the possible efficiency of even still not synthesised ligands, making the pre-selection of compounds much easy and faster.
Export Options
About this article
Cite this article as:
Ruiz M. F. and Grigera R. J., Free Energy Perturbation Calculations on Glucosidase-Inhibitor Complexes, Medicinal Chemistry 2005; 1 (5) . https://dx.doi.org/10.2174/1573406054864151
DOI https://dx.doi.org/10.2174/1573406054864151 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Bullous Pemphigoid and Neurologic Diseases: Toward a Specific Serologic Profile?
Endocrine, Metabolic & Immune Disorders - Drug Targets Novel Approaches to the Therapy of Rheumatoid Arthritis based on an Understanding of Disease Mechanisms
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Neonatal Hypertension: An Underdiagnosed Condition, A Review Article
Current Hypertension Reviews Interleukin-18: Biology and Role in the Immunotherapy of Cancer
Current Medicinal Chemistry Protein-C Reactive as Biomarker Predictor of Schizophrenia Phases of Illness? A Systematic Review
Current Neuropharmacology Three-dimensional Printing-Driving Liver Therapies
Current Medicinal Chemistry Prognostic Markers in Small Cell Lung Cancer
Current Cancer Therapy Reviews Is Alzheimers Disease a Myth? When is Disease a Disease?
Current Alzheimer Research Neurotrophic and Neuroprotective Effects of Muscle Contraction
Current Pharmaceutical Design In vitro Generated Mesenchymal Stem Cells: Suitable Tools to Target Insulin Dependent Diabetes Mellitus?
Current Stem Cell Research & Therapy Tau as a Therapeutic Target for Alzheimers Disease
Current Alzheimer Research Natural Polymer-based Stimuli-responsive Hydrogels
Current Medicinal Chemistry Antiprotozoal Agents: An Overview
Anti-Infective Agents in Medicinal Chemistry Diabetes Mellitus and SARS-CoV-2 Infection: Pathophysiologic Mechanisms and Implications in Management
Current Diabetes Reviews Beta Blockers can Mask not only Hypoglycemia but also Hypotension
Current Pharmaceutical Design Evaluation of Insulin Resistance Induced Brain Tissue Dysfunction in Obese Dams and their Neonates: Role of Ipriflavone Amelioration
Combinatorial Chemistry & High Throughput Screening Cytochrome P450 in the Brain ; A Review
Current Drug Metabolism A Case Report: Euglycemic Diabetic Ketoacidosis Presenting as Chest Pain in a Patient on a Low Carbohydrate Diet
Current Diabetes Reviews CYP Epoxygenase Derived EETs: From Cardiovascular Protection to Human Cancer Therapy
Current Topics in Medicinal Chemistry Jumping on the Train of Personalized Medicine: A Primer for Non- Geneticist Clinicians: Part 3. Clinical Applications in the Personalized Medicine Area
Current Psychiatry Reviews