Computer-aided design of amino acid-based therapeutics: a review

Farhadi, Tayebeh; Hashemian, Seyed MohammadReza

Computer-aided design of amino acid-based therapeutics Fixing the backbone decreases the computational complication, but it may inhibit the main chain modifications to adjust sequence alternation. 7 Backbone flexibility can generate designed functionalities over the protein's normal function. The backbone flexibility is introduced through incorporating other closely associated conformations to an existing structure. [40] [41] [42] Recently, new functionalities were effectively introduced into the TIM-barrel topology. 43 This fold has been detected as one of the most shared structures in 21 distinct protein superfamilies. 44 Sequence search and characterization In a design procedure, a protein sequence is selected such that it meets the energetic and geometric constraints established by the chosen fold. Sequence search techniques sample different sequences and estimate their energies to gain the one owing the minimum energy. 3 In order to identify the sequences subject to an objective function or a specific energy, a diverse strategies including optimization and probabilistic approaches have been developed. 45 Optimization processes may recognize candidate sequences using stochastic or deterministic methods. 45 Probabilistic approaches focus on characterizing the sequence space probabilistically.