Simulation Studies on the Lipid Interaction and Conformation of Novel Drug-Delivery Pseudopeptidic Polymers
File(s)
Accepted version
Supporting information
Author(s)
Wang, S
Bresme, F
Type
Journal Article
Abstract
Pseudopeptides based on poly(l-lysine isophthalamide) backbone have emerged as promising drug delivery candidates due to their pH-activated membrane disruption ability. To gain molecular understanding on these novel polymeric species, we have constructed force-field parameters and simulated the behaviors of polymers with and without phenylalanine grafted as side chains under conditions compatible with different pHs. The free energy changes upon polymer permeation through membrane were calculated using the umbrella sampling technique. We show that both polymers with and without grafts interact better with the membrane under conditions compatible with lower pH. The conformational states of the polymers were investigated in water and at a water–membrane interface. On the basis of Markov state modeling results, we propose a possible advantage of the grafted polymer over the ungrafted polymer for membrane rupture because of its quicker conformational rearrangement kinetics.
Date Issued
2017-09-04
Date Acceptance
2017-09-03
Citation
JOURNAL OF PHYSICAL CHEMISTRY B, 2017, 121 (39), pp.9113-9125
ISSN
1520-6106
Publisher
American Chemical Society
Start Page
9113
End Page
9125
Journal / Book Title
JOURNAL OF PHYSICAL CHEMISTRY B
Volume
121
Issue
39
Copyright Statement
© 2017 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Physical Chemistry B, after peer review and technical editing by the publisher. To access the final edited and published work see https://dx.doi.org/10.1021/acs.jpcb.7b06562
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000412718600004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Physical Sciences
Chemistry, Physical
Chemistry
MOLECULAR-DYNAMICS SIMULATIONS
COARSE-GRAINED MODEL
INTRACELLULAR DELIVERY
PORE FORMATION
MARKOV-MODELS
FORCE-FIELD
BILAYERS
MEMBRANES
PEPTIDES
KINETICS
03 Chemical Sciences
09 Engineering
02 Physical Sciences
Publication Status
Published