Significance of unfolding thermodynamics for predicting aggregation kinetics: a case study on high concentration solutions of a multi-domain protein.

Purpose: To enable aggregation rate prediction over a broad temperature range for complex multi-domain proteins at high concentrations.

Methods: Thermal unfolding, non-isothermal kinetics and storage stability studies were conducted on a model multi-domain protein (MDP) at moderate to high concentrations (25-125 mg/mL) over a broad temperature range (4-40°C).

Results: Storage stability studies indicated the aggregation of MDP in solution to be a second order process.

Effect of the design of the stopper including dimension, type, and vent area on lyophilization process.

Unlabelled: The objective of this study was to examine the role of dimension and design of stoppers on the vapor transfer rate during the lyophilization process. Glass vials (100 cc, 28-mm neck diameter) containing mannitol solutions (4% w/w) were fitted with specially designed Teflon discs with circular holes (area ranging 0.12 to 41.

Effect of cosolvents on the adsorption of peptides at the solid-liquid interface.

The adsorption of a peptide at solid surfaces is the result of a complex interplay of interactions between the peptide, solvent, and surface. In this work, Monte Carlo simulations were performed to evaluate the effect of the solvent hydrogen bonding ability on the adsorption of the peptide ASP(1)-ASP(2)-ILE(3)-ILE(4)-ASP(5)-ASP(6)-ILE(7)-ILE(8) at a charged surface consisting of CH(2) atoms with a fixed lattice arrangement. Various water-alcohol mixtures were used as solvent because alcohols are known to alter the dielectric constant, hydrophobicity, and hydrogen bonding capacity of water.

Conformational changes of peptides at solid/liquid interfaces: a Monte Carlo study.

Monte Carlo simulations were performed to study the conformational changes of negatively charged model peptides dissolved in water adsorbed onto charged surfaces. 8-, 16-, and 20-residues peptides were used, each of them consisted of repeating diblock units of aspartic acid (ASP, polar amino acid) and isoleucine (ILE, nonpolar amino acid) residues. We found that a water patch was retained at the charged surface, separating the peptide from it.

Computer simulations and neutron reflectivity of proteins at interfaces.

Computer simulations in conjunction with neutron reflectivity is an excellent combination for the study of biological materials at solid-liquid interfaces: Both techniques have excellent resolution levels (Angströms) and they are mature. A stronger interaction between physicists and biologists will allow the use of these two approaches in topics of biological-biomedical interest.