Abstract
The problem of incorporating receptor flexibility in routine in silico screening of databases of small chemical compounds for the purposes of structure based drug design is still an unsolved problem. The main reason behind this difficulty is the large number of degrees of freedom that have to be considered to represent receptor flexibility. In this paper we review protein flexibility models that have been developed to limit the number of additional search parameters. These models can be roughly divided into five different categories. These are a) use of soft receptors which relax energetic penalties due to steric clashes, b) selection of a few critical degrees of freedom in the receptor binding site, c) use of multiple receptor structures either individually or by combining them using an averaging scheme, d) use of modified molecular simulation methods, and e) use of collective degrees of freedom as a new basis of representation for protein flexibility. All these flexible receptor models strive to balance an improvement in the accuracy of the binding predictions with an increase in computational cost. In addition, other challenges such as the development of accurate solvation models and scoring functions make the receptor flexibility problem even harder.
Keywords: Conformational Flexibility Models
Current Pharmaceutical Design
Title: Conformational Flexibility Models for the Receptor in Structure Based Drug Design
Volume: 9 Issue: 20
Author(s): M. L. Teodoro and L. E. Kavraki
Affiliation:
Keywords: Conformational Flexibility Models
Abstract: The problem of incorporating receptor flexibility in routine in silico screening of databases of small chemical compounds for the purposes of structure based drug design is still an unsolved problem. The main reason behind this difficulty is the large number of degrees of freedom that have to be considered to represent receptor flexibility. In this paper we review protein flexibility models that have been developed to limit the number of additional search parameters. These models can be roughly divided into five different categories. These are a) use of soft receptors which relax energetic penalties due to steric clashes, b) selection of a few critical degrees of freedom in the receptor binding site, c) use of multiple receptor structures either individually or by combining them using an averaging scheme, d) use of modified molecular simulation methods, and e) use of collective degrees of freedom as a new basis of representation for protein flexibility. All these flexible receptor models strive to balance an improvement in the accuracy of the binding predictions with an increase in computational cost. In addition, other challenges such as the development of accurate solvation models and scoring functions make the receptor flexibility problem even harder.
Export Options
About this article
Cite this article as:
Teodoro L. M. and Kavraki E. L., Conformational Flexibility Models for the Receptor in Structure Based Drug Design, Current Pharmaceutical Design 2003; 9 (20) . https://dx.doi.org/10.2174/1381612033454595
DOI https://dx.doi.org/10.2174/1381612033454595 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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