Abstract
A significant portion of recent drug development efforts has been focused on protein kinases. More than a hundred different compounds are currently under clinical trials and nearly 30% of all the scientific articles in drug discovery are on protein kinase inhibitors. Protein kinases are very flexible targets and undergo significant conformational changes upon activation and during the catalytic cycle. This flexibility can be exploited in drug discovery. Some of the inactive states that emerge during the conformational changes are targeted by various inhibitors with a significant gain in selectivity. Here, we review the recent advances being made in understanding the details and the mechanism of these conformational changes thanks to the progress in molecular dynamics and free energy algorithms as well as to the availability of specialized computer hardware.
Keywords: Kinase, imatinib, molecular dynamics, metadynamics, allostery, signaling
Current Topics in Medicinal Chemistry
Title:New Insights in Protein Kinase Conformational Dynamics
Volume: 12 Issue: 17
Author(s): Giorgio Saladino and Francesco Luigi Gervasio
Affiliation:
Keywords: Kinase, imatinib, molecular dynamics, metadynamics, allostery, signaling
Abstract: A significant portion of recent drug development efforts has been focused on protein kinases. More than a hundred different compounds are currently under clinical trials and nearly 30% of all the scientific articles in drug discovery are on protein kinase inhibitors. Protein kinases are very flexible targets and undergo significant conformational changes upon activation and during the catalytic cycle. This flexibility can be exploited in drug discovery. Some of the inactive states that emerge during the conformational changes are targeted by various inhibitors with a significant gain in selectivity. Here, we review the recent advances being made in understanding the details and the mechanism of these conformational changes thanks to the progress in molecular dynamics and free energy algorithms as well as to the availability of specialized computer hardware.
Export Options
About this article
Cite this article as:
Saladino Giorgio and Luigi Gervasio Francesco, New Insights in Protein Kinase Conformational Dynamics, Current Topics in Medicinal Chemistry 2012; 12 (17) . https://dx.doi.org/10.2174/156802612804547407
DOI https://dx.doi.org/10.2174/156802612804547407 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
- Announcements
Related Articles
-
Current Pharmacological Approaches to Prevent and Treat Post- Menopausal Osteoporosis
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Microporation Techniques for Enhanced Delivery of Therapeutic Agents
Recent Patents on Drug Delivery & Formulation Diabetic Neuropathy: Update on Pathophysiological Mechanism and the Possible Involvement of Glutamate Pathways
Current Diabetes Reviews Cerebral Malaria - A Neurovascular Pathology with Many Riddles Still to be Solved
Current Neurovascular Research Changes in Immune and Endocrine Systems in Scrapie-Infected Animals
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Editorial [ Endothelial Dysfunction: Novel Therapeutic Approaches (Guest Editor: Dimitris Tousoulis)]
Current Vascular Pharmacology Subcellular Analysis of the Platelet Proteome
Current Proteomics Preventing Type 2 Diabetes Mellitus: Room for Residual Risk Reduction After Lifestyle Changes?
Current Pharmaceutical Design Harnessing CD36 to Rein in Inflammation
Endocrine, Metabolic & Immune Disorders - Drug Targets Editorial [Hot Topic: Novel Peptides and Proteins in Diabetes Mellitus (Guest Editors: Po Sing Leung and Marc de Gasparo)]
Current Protein & Peptide Science The Leukocyte Common Antigen-Related Protein LAR: Candidate PTP for Inhibitory Targeting
Current Topics in Medicinal Chemistry Chlamydia-Secreted Proteins in Chlamydial Interactions with Host Cells
Current Chemical Biology [18F]Fluoroalkyl Agents: Synthesis, Reactivity and Application for Development of PET Ligands in Molecular Imaging
Current Topics in Medicinal Chemistry A Synopsis on the Role of Tyrosine Hydroxylase in Parkinson’s Disease
CNS & Neurological Disorders - Drug Targets Recent Developments in Nanomedicines for Management of Various Health Issues Via Metabolism and Physico-Chemical Properties
Current Drug Metabolism Role of Chymase in Preeclampsia
Current Vascular Pharmacology Wide Pulse Pressure in the Elderly
Current Cardiology Reviews Palmitoylethanolamide Relieves Pain and Preserves Pancreatic Islet Cells in a Murine Model of Diabetes
CNS & Neurological Disorders - Drug Targets Atherosclerosis as an Inflammatory Disease
Current Pharmaceutical Design microRNAs-based Predictor Factor in Patients with Migraine-ischemic Stroke
MicroRNA