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
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Alcoholisms Evolutionary and Cultural Origins
Current Drug Abuse Reviews Glucose Lowering Activity of the Aqueous Extract of Warionia saharae in Normal and Diabetic Rats
Cardiovascular & Hematological Agents in Medicinal Chemistry β-amyloid and Oxidative Stress: Perspectives in Drug Development
Current Pharmaceutical Design All for Statins and Statins for All; An Update
Current Pharmaceutical Design Mitigating Perspectives of Asiatic Acid in the Renal Derangements of Streptozotocin-Nicotinamide Induced Diabetic Rats
Cardiovascular & Hematological Agents in Medicinal Chemistry KRAB-Zinc Finger Proteins: A Repressor Family Displaying Multiple Biological Functions
Current Genomics PI3K Inhibitors for Cancer Therapy: What has been Achieved So Far?
Current Medicinal Chemistry Effects of Exercise on Physical and Mental Health, and Cognitive and Brain Functions in Schizophrenia: Clinical and Experimental Evidence
CNS & Neurological Disorders - Drug Targets How Satiety Factors Reach CNS Appetite Centers
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Cardiovascular Risk Prediction using JBS3 Tool: A Kerala based Study
Current Medical Imaging Genetic Alterations in Differentiated Thyroid Cancers
Endocrine, Metabolic & Immune Disorders - Drug Targets Insulin Modulates <i>In Vitro Secretion</i> of Cytokines and Cytotoxins by Human Glial Cells
Current Alzheimer Research An Overview of Nanoformulated Nutraceuticals and their Therapeutic Approaches
Current Nutrition & Food Science Management of Primary Aldosteronism: Its Complications and Their Outcomes After Treatment
Current Vascular Pharmacology Effects of Peroxyl Radicals on Contractility of Rabbit Aorta and Guinea Pig Atria
Endocrine, Metabolic & Immune Disorders - Drug Targets Homeostasis and Compensatory Homeostasis: Bridging Western Medicine and Traditional Chinese Medicine
Current Cardiology Reviews Selective Peroxisome Proliferator-Activated Receptor-γ Modulation to Reduce Cardiovascular Risk in Patients with Insulin Resistance
Recent Patents on Cardiovascular Drug Discovery New Target Molecules in the Drug Control of Blood Pressure and Circulation
Current Drug Targets - Cardiovascular & Hematological Disorders Pericyte Loss in Diabetic Retinopathy: Mechanisms and Consequences
Current Medicinal Chemistry Perceived Barriers, Benefits, Facilitators, and Attitudes of Health Professionals Towards Multidisciplinary Team Care in Type 2 Diabetes Management: A Systematic Review
Current Diabetes Reviews