Abstract
BackgroundIt is well known the strong relationship between protein structure and flexibility, on one hand, and biological protein function, on the other hand. Technically, protein flexibility exploration is an essential task in many applications, such as protein structure prediction and modeling. In this contribution we have compared two different approaches to explore the flexibility space of protein domains: i) molecular dynamics (MD-space), and ii) the study of the structural changes within superfamily (SF-space).ResultsOur analysis indicates that the MD-space and the SF-space display a significant overlap, but are still different enough to be considered as complementary. The SF-space space is wider but less complex than the MD-space, irrespective of the number of members in the superfamily. Also, the SF-space does not sample all possibilities offered by the MD-space, but often introduces very large changes along just a few deformation modes, whose number tend to a plateau as the number of related folds in the superfamily increases.ConclusionTheoretically, we obtained two conclusions. First, that function restricts the access to some flexibility patterns to evolution, as we observe that when a superfamily member changes to become another, the path does not completely overlap with the physical deformability. Second, that conformational changes from variation in a superfamily are larger and much simpler than those allowed by physical deformability. Methodologically, the conclusion is that both spaces studied are complementary, and have different size and complexity. We expect this fact to have application in fields as 3D-EM/X-ray hybrid models or ab initio protein folding.
Highlights
It is well known the strong relationship between protein structure and flexibility, on one hand, and biological protein function, on the other hand
A similar reasoning explains it: a greater size of the superfamily implies a parallel increase in the possibilities of sequence variation, while it does not affect the variance of the molecular dynamics (MD)-space
We do not find any relationship between the variance of the MD-space and the number of aminoacids of the domain, which can be explained considering that the factors producing more structural variability, such as flexible loops, are not affected by the size of a domain
Summary
It is well known the strong relationship between protein structure and flexibility, on one hand, and biological protein function, on the other hand. Protein flexibility exploration is an essential task in many applications, such as protein structure prediction and modeling. The connection between sequence and structure has centered a great amount of work and detailed theories of protein folding exist [1], but still predicting structure or function from sequence is a extremely complex task except in cases of high sequence identity between the target protein and a well annotated homolog [2]. There are many cases of non-homologous proteins sharing a given fold or function as well as proteins with reasonably similar sequences having quite different structures. Still less information exists on this connection between flexibility and function and, regarding the conformational changes that need to happen in a protein to perform its biological function [3,4,5]. In the very same way as structures that are able to perform a specific function are conserved by evolution by not tolerating mutations that seriously modify that structure, it is plausible to think that mutations disrupting the flexibility pattern of a given protein are not going to be accepted either [3,6,7,8,9]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.