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Content archived on 2024-06-18

Integrated protein evolution model

Objective

Proteins evolve to highly diverged sequence, function and structure. The dynamics of protein evolution is fundamental for understanding how natural protein evolve, and also for creating new proteins in the laboratory for medical and industrial use. “Epistasis”, which is the interaction between the effects of mutations, is often observed in nature and is the central to understand the dynamics of evolution, because it shapes the passages in the evolution. However, epistasis has been considered to be a quite complicated phenomenon and difficult to predict, thus it seemed that the dynamics of protein evolution was difficult to understand. In this project, I propose a new integrated protein evolution model which describes the fitness of protein from the physico-chemical properties of proteins. In this model, the structure of the fitness cause of epistasis of the fitness even though there is no interaction between the effects of mutations in physico-chemical properties; The fitness of protein (enzymatic activity in the cell: v0) is multiplication of function (enzymatic activity: kcat/KM) and fraction of functional expression level of protein (enzyme concentration: [E]). And the fraction of functional expression level is non-linearly correlated to the stability of proteins (∆∆G) due to unfolding, aggregation, degradation of proteins. This model will provide a new insight of epistasis and enable us to predict and understand the dynamics of protein evolution. I will validate and refine the model comparing the experimental evolution experiments. Furthermore, I will apply this model to analyze mono-genetic disease related proteins to establish the way to diagnose potential patients. This integrated protein evolution model will revolutionize the way how we study the dynamics of protein evolution, innovate the methodology of directed evolution, and make significant impact on the study of the network and biological evolution.

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Keywords

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Topic(s)

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Call for proposal

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FP7-PEOPLE-IEF-2008
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
EU contribution
€ 173 568,66
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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