Introduction to the Roadmap of Future Medicine: The Physiological Fitness Landscape

2021 ◽  
pp. 245-306
Author(s):  
Brian Fertig
2021 ◽  
Vol 7 (6) ◽  
pp. 1-14
Author(s):  
Deepak Chopra ◽  

Using methods first developed in the physical sciences and adapting them to medicine and physiology, as is proposed here regarding the Physiological Fitness Landscape, can be a powerful tool in the management of disease and in the maintenance of long health span.


10.26524/1424 ◽  
2014 ◽  
Vol 3 (2) ◽  
pp. 43-51
Author(s):  
Gurmej Singh Dhaliwal ◽  
Baljinder Singh Bal ◽  
Pritam Singh ◽  
Davinder Singh

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carlos G. Acevedo-Rocha ◽  
Aitao Li ◽  
Lorenzo D’Amore ◽  
Sabrina Hoebenreich ◽  
Joaquin Sanchis ◽  
...  

AbstractMultidimensional fitness landscapes provide insights into the molecular basis of laboratory and natural evolution. To date, such efforts usually focus on limited protein families and a single enzyme trait, with little concern about the relationship between protein epistasis and conformational dynamics. Here, we report a multiparametric fitness landscape for a cytochrome P450 monooxygenase that was engineered for the regio- and stereoselective hydroxylation of a steroid. We develop a computational program to automatically quantify non-additive effects among all possible mutational pathways, finding pervasive cooperative signs and magnitude epistasis on multiple catalytic traits. By using quantum mechanics and molecular dynamics simulations, we show that these effects are modulated by long-range interactions in loops, helices and β-strands that gate the substrate access channel allowing for optimal catalysis. Our work highlights the importance of conformational dynamics on epistasis in an enzyme involved in secondary metabolism and offers insights for engineering P450s.


2016 ◽  
Vol 33 (5) ◽  
pp. 1378-1378 ◽  
Author(s):  
Elad Firnberg ◽  
Jason W. Labonte ◽  
Jeffrey J. Gray ◽  
Marc Ostermeier

2014 ◽  
Vol 22 (1) ◽  
pp. 159-188 ◽  
Author(s):  
Mikdam Turkey ◽  
Riccardo Poli

Several previous studies have focused on modelling and analysing the collective dynamic behaviour of population-based algorithms. However, an empirical approach for identifying and characterising such a behaviour is surprisingly lacking. In this paper, we present a new model to capture this collective behaviour, and to extract and quantify features associated with it. The proposed model studies the topological distribution of an algorithm's activity from both a genotypic and a phenotypic perspective, and represents population dynamics using multiple levels of abstraction. The model can have different instantiations. Here it has been implemented using a modified version of self-organising maps. These are used to represent and track the population motion in the fitness landscape as the algorithm operates on solving a problem. Based on this model, we developed a set of features that characterise the population's collective dynamic behaviour. By analysing them and revealing their dependency on fitness distributions, we were then able to define an indicator of the exploitation behaviour of an algorithm. This is an entropy-based measure that assesses the dependency on fitness distributions of different features of population dynamics. To test the proposed measures, evolutionary algorithms with different crossover operators, selection pressure levels and population handling techniques have been examined, which lead populations to exhibit a wide range of exploitation-exploration behaviours.


2014 ◽  
Vol 22 (3) ◽  
pp. 361-403 ◽  
Author(s):  
F. V. C. Martins ◽  
E. G. Carrano ◽  
E. F. Wanner ◽  
R. H. C. Takahashi ◽  
G. R. Mateus ◽  
...  

Recent works raised the hypothesis that the assignment of a geometry to the decision variable space of a combinatorial problem could be useful both for providing meaningful descriptions of the fitness landscape and for supporting the systematic construction of evolutionary operators (the geometric operators) that make a consistent usage of the space geometric properties in the search for problem optima. This paper introduces some new geometric operators that constitute the realization of searches along the combinatorial space versions of the geometric entities descent directions and subspaces. The new geometric operators are stated in the specific context of the wireless sensor network dynamic coverage and connectivity problem (WSN-DCCP). A genetic algorithm (GA) is developed for the WSN-DCCP using the proposed operators, being compared with a formulation based on integer linear programming (ILP) which is solved with exact methods. That ILP formulation adopts a proxy objective function based on the minimization of energy consumption in the network, in order to approximate the objective of network lifetime maximization, and a greedy approach for dealing with the system's dynamics. To the authors’ knowledge, the proposed GA is the first algorithm to outperform the lifetime of networks as synthesized by the ILP formulation, also running in much smaller computational times for large instances.


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