An Intra-Company Analysis of Inherent Particles in Biologicals Shapes the Protein Particle Mitigation Strategy Across Development Stages.

To better understand protein aggregation and inherent particle formation in the biologics pipeline at Novartis, a cross-functional team collected and analyzed historical protein particle issues. Inherent particle occurrences from the past 10 years were systematically captured in a protein particle database. Where the root cause was identified, a number of product attributes (such as development stage, process step, or protein format) were trended.

On the structure and dynamics of the hydrated sulfite ion in aqueous solution--an ab initio QMCF MD simulation and large angle X-ray scattering study.

Theoretical ab initio quantum mechanical charge field molecular dynamics (QMCF MD) formalism has been applied in conjunction to experimental large angle X-ray scattering to study the structure and dynamics of the hydrated sulfite ion in aqueous solution. The results show that there is a considerable effect of the lone electron-pair on sulfur concerning structure and dynamics in comparison with the sulfate ion with higher oxidation number and symmetry of the hydration shell. The S-O bond distance in the hydrated sulfite ion has been determined to 1.

Structure and dynamics of the UO2+ ion in aqueous solution: an ab initio QMCF-MD study.

The quantum mechanical charge field molecular dynamics (QMCF-MD) framework was applied in a simulation of the uranyl(v) ion in aqueous solution. The structure was evaluated on the basis of overall and sectorial radial distribution functions, angular distribution functions, tilt- and Theta-angle distribution functions and coordination number distributions. The cation is strongly coordinated by 4 water ligands at an average distance of 2.

Structure and dynamics of the chromate ion in aqueous solution. An ab initio QMCF-MD simulation.

An ab initio quantum-mechanical charge-field molecular-dynamics (QMCF-MD) simulation of the chromate ion in aqueous solution at ambient temperature was performed to study the structure and dynamics of this ion and its hydration shell. In contrast to conventional quantum-mechanical molecular-mechanics molecular-dynamics (QM/MM-MD) simulations, the QMCF-MD approach offers the possibility of investigating composite systems with the accuracy of a QM/MM method but without the time-consuming construction of solute-solvent potential functions. The data of the simulation give a clear picture of the first hydration shell of the chromate anion, which consists of 14 water molecules.

A quantum mechanical charge field molecular dynamics study of Fe(2+) and Fe(3+) ions in aqueous solutions.

Ab initio quantum mechanical charge field molecular dynamics (QMCF-MD) simulations have been performed for aqueous solutions of Fe(2+) and Fe(3+) ions at the Hartree-Fock level of theory to describe and compare their structural and dynamical behavior. The structural features of both hydrated ions are characterized by radial distribution functions that give the maximum probability of the ion-O distance for Fe(2+) and Fe(3+) ions at 2.15 and 2.

Hydrolytic conversion of AsO(-3)4 to HAsO(-2)4: a QMCF MD study.

A quantum mechanical charge field molecular dynamics (QMCF MD) study of AsO in water was carried out to gain insight into its conversion from the hydrated anion resulting in OH(-) ions and HAsO, which occurs on the scale of a few hundred femtoseconds. The OH(-) ion undergoes further proton exchange with water molecules, while HAsO is a stable species.

Structural and dynamic aspects of hydration of HAsO4(-2): an ab initio QMCF MD simulation.

An ab initio quantum mechanical charge field simulation has been carried out in order to obtain molecular level insight into the hydration behavior of HAsO4(-2), one of the major biologically active components of As(V) oxoanion in neutral to slightly alkaline aqueous medium. Moreover, a geometrical definition of hydrogen bonding has been used to probe and characterize both solute-solvent and solvent-solvent hydrogen bonding present in the system. The asymmetry of the anion induced by the protonation of one of the oxygens of the arsenate anion causes rather irregular hydration structure.

Temperature dependence of structure and dynamics of the hydrated Ca2+ ion according to ab initio quantum mechanical charge field and classical molecular dynamics.

Simulations using ab initio quantum mechanical charge field molecular dynamics (QMCF MD) and classical molecular dynamics using two-body and three-body potentials were performed to investigate the hydration of the Ca(2+) ion at different temperatures. Results from the simulations demonstrate significant effects of temperature on solution dynamics and the corresponding composition and structure of hydrated Ca(2+). Substantial increase in ligand exchange events was observed in going from 273.

Revisiting the hydration of Pb(II): a QMCF MD approach.

A quantum mechanical charge field (QMCF) molecular dynamics (MD) study of Pb(II) in an aqueous medium was carried out in order to gain insight into its solvation behavior, for both structural and dynamic aspects. Applying the advanced methodology and different basis sets, some new aspects concerning the solvation of Pb(II) have been revealed. One of the most interesting outcomes of the current simulation is the variation of first shell coordination number from 7 to 9 in the Pb(H2O)n(2+) complex with Pb(H2O)8(2+) as a major species.

Structure and dynamics of the UO(2)(2+) ion in aqueous solution: an ab initio QMCF MD study.

A comprehensive theoretical investigation on the structure and dynamics of the UO(2)(2+) ion in aqueous solution using double-zeta HF level quantum mechanical charge field molecular dynamics is presented. The quantum mechanical region includes two full layers of hydration and is embedded in a large box of explicitly treated water to achieve a realistic environment. A number of different functions, including segmential, radial, and angular distribution functions, are employed together with tilt- and Theta-angle distribution functions to describe the complex structural properties of this ion.

Beryllium(II): the strongest structure-forming ion in water? A QMCF MD simulation study.

A quantum mechanical charge field (QMCF) molecular dynamics (MD) simulation including the first and second hydration shells in the QM region has been carried out to describe the structural and dynamical properties of Be(2+) in aqueous solution. In this methodology, the full first and second hydration shells are treated by ab initio quantum mechanics supplemented by a fluctuating electrostatic embedding technique. From the simulation, structural properties were extracted and were found to be in good agreement with previously published experimental and theoretical results.

Ab initio quantum mechanical charge field study of hydrated bicarbonate ion: structural and dynamical properties.

The ab initio quantum mechanical charge field molecular dynamics (QMCF MD) formalism was applied to simulate the bicarbonate ion, HCO(3)(-), in aqueous solution. The difference in coordination numbers obtained by summation over atoms (6.6) and for the solvent-accessible surface (5.

Structure and dynamics of the U4+ ion in aqueous solution: an ab initio quantum mechanical charge field molecular dynamics study.

The structure and dynamics of the stable four-times positively charged uranium(IV) cation in aqueous solution have been investigated by ab initio quantum mechanical charge field (QMCF) molecular dynamics (MD) simulation at the Hartree-Fock double-zeta quantum mechanical level. The QMCF-MD approach enables investigations with the accuracy of a quantum mechanics/molecular mechanics approach without the need for the construction of solute-solvent potentials. Angular distribution functions; radial distribution functions; coordination numbers of the first, second, and third shell (9, 19, and 44, respectively); coordination number distribution functions; tilt- and Theta-angle distribution functions; as well as local density corrected triangle distribution functions have been employed for the evaluation of the hydrated ion's structure.

The hydration structure of Sn(II): an ab initio quantum mechanical charge field molecular dynamics study.

The structural properties of the hydrated Sn(2+) ion have been investigated using ab initio quantum mechanical charge field molecular dynamics (QMCF MD) simulations at double-xi HF quantum mechanical level. The results from the work significantly extend previous study using QM/MM MD simulation and are in good agreement with X-Ray and EXAFS diffraction experiments. The data indicate a set of characteristics for the first hydration shell uncommon among metal ions.

Structure and dynamics of phosphate ion in aqueous solution: an ab initio QMCF MD study.

A simulation of phosphate in aqueous solution was carried out employing the new QMCF MD approach which offers the possibility to investigate composite systems with the accuracy of a QMMM method but without the time consuming creation of solute-solvent potential functions. The data of the simulations give a clear picture of the hydration shells of the phosphate anion. The first shell consists of 13 water molecules and each oxygen of the phosphate forms in average three hydrogens bonds to different solvent molecules.

Structure and dynamics of solvated Sn(II) in aqueous solution: an ab initio QM/MM MD approach.

Structural and dynamical properties of the hydrated Sn(II) ion have been investigated by ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations at double-zeta HF quantum mechanical level. The results indicate Sn(II)aq to be a rather peculiar, if not unique, case of a hydrated ion: four of its eight first-shell ligands do not take place in the otherwise frequent ligand-exchange processes, forming an approximately tetrahedral cage around the ion. The remaining ligands, however, exchange at a rate that is rather comparable to monovalent than divalent ions.