Rational design of type-IA receptor-derived cyclic peptides to target human bone morphogenic protein 2.
Rational design of type-IA receptor-derived cyclic peptides to target human bone morphogenic protein 2.
J Biosci. 2019 Dec;44(6):
Authors: Fan X, Xia H, Liu X, Li B, Fang J
Abstract
Human bone morphogenetic protein 2 (BMP2) is a bone-growth regulatory factor involved in the formation of bone and cartilage, and has been recogn ized as an attractive therapeutic target for a variety of bone diseases and defects. Here, we report successful design of a head-to-tail cyclic peptide based on crystal structure to target BMP2. Computational alanine scanning identifies two hotspot regions at the crystal complex interface of BMP2 with its type-IA receptor; promising one is stripped from the interface to derive a linear self-inhibitory peptide RPS2[r78-94] that covers residues 78-94 of the receptor protein. Dynamics simulation and energetics analysis reveal that the peptide is highly flexible in isolated state and cannot spontaneously bind to BMP2. The RPS2[r78-94] peptide is further extended from its N- and C-termini until reaching two spatially vicinal residues 74 and 98 in the crystal structure of intact BMP2-receptor complex system, consequently resulting in a longer peptide RPS2[r74-98], which is then cyclized in a head-to-tail manner to obtain its cyclic counterpart cycRPS2[r74-98]. Computational analysis suggests that the cyclic peptide can well maintain in a conformation similar with its active conformation in complex crystal structure, e...
Source: Journal of Biosciences - Category: Biomedical Science Authors: Fan X, Xia H, Liu X, Li B, Fang J Tags: J Biosci Source Type: research
More News: Biomedical Science | PET Scan