Water Distribution on Protein Surface of the Lyophilized Proteins with Different Topography Studied by Molecular Dynamics Simulations

Shaoxin Feng*, Günther H. J. Peters, Evgenyi Shalaev

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Water play an important role in many structural and physicochemical properties of lyophilized proteins. Molecular dynamics simulations were employed to study the explicit water distributions on four structurally diversed proteins: insulin-like growth factor 1 (IGF1), immunoglobin G1 (IgG1), human serum albumin (HSA), and collagen. The MD simulations were combined with the literature data on water vapor sorption isotherms. To account for the heterogeneity of protein surface, the water molecules were classified into different groups according to the binding strengths. A mechanistic mathematical model was built to describe the type-II vapor sorption isotherms and successfully applied to all four model protein systems. Although commonly used Brunauer-Emmett-Teller (BET) theory has a good fitting to the experimental vapor sorption isotherms, the basic "monolayer" concept is not consistent with reality - covering too limited protein surface. Experimentally, several physicochemical properties did show a break point near the BET "monolayer" level. This study demonstrates the water content threshold or BET "monolayer" is consistent with the onset of water cluster (n≥3) formation. Based on water distributions at different amino acid sidechains as well as the backbones, a simple formula was derived based on primary sequence and fractions of ordered secondary structures (i.e. alpha helix and beta sheet) to predict the BET "monolayer". We find that proteins with helical structural elements are more stable upon changes in water content compared to other protein architectures.
Original languageEnglish
JournalJournal of Pharmaceutical Sciences
ISSN0022-3549
DOIs
Publication statusAccepted/In press - 2022

Keywords

  • Proteins
  • Water sorption
  • Molecular dynamics
  • Mathematical model
  • Protein structure
  • Physicochemical properties

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