Aggregation of therapeutic monoclonal antibodies (mAbs) can negatively affect their chemistry, manufacturing and control attributes and lead to undesirable immune responses in patients. Therefore, optimization of lead Monoclonal antibody (mAb) drug candidates during discovery stages to mitigate aggregation is increasingly becoming an integral part of their developability assessments. The disruption of short sequence motifs called Aggregation prone regions (APRs) found in amino acid sequences of mAb candidates can potentially mitigate their aggregation. In this work, we have performed Molecular Dynamics (MD) simulations to study the aggregation of an APR (VLVIY) found in λ light chains of human antibodies and its single point mutant KLVIY. Eighteen different multi-copy peptide simulation systems of ‘VLVIY’ and ‘KLVIY’ were constructed by varying their concentrations, temperatures, termini capping, and flanking gate-keeper regions. Within 20 ns of the simulation, peptide ‘VLVIY’ formed an aggregate of 100 peptides at ~0.1 M concentration with a 60% reduction in solvent accessible surface area (SASA). Further, analysis of the SASA change, peptide cluster distribution, and water residence time demonstrated how Val➔Lys mutation resists aggregation and improves solubility. Presence of Lys slows down aggregation kinetics via charge-charge repulsions and by raising the kinetic barrier to formation of large oligomers. However, the effect of the Val ➔ Lys mutation is dependent on sequence and structural contexts around the APR. This mutation also alters the solvation shell around the peptide by favoring solute-solvent interactions, thereby increasing its solubility. This work has provided a detailed mechanistic explanation of how APR disruption can mitigate aggregation in biotherapeutics and improve their developability.