Modifying amino acids that are important for the antimicrobial activity of a peptide could potentially decrease its activity. The activity of an antimicrobial peptide (AMP) depends on various factors, including its primary sequence, conformation, and surface charge. Modifying amino acids in the peptide may alter these factors, leading to changes in its activity.
For example, modifying amino acids that contribute to the positive charge of the AMP may alter its interaction with the negatively charged bacterial cell membrane, potentially decreasing its antimicrobial activity. Similarly, modifications that alter the conformation of the AMP may affect its ability to insert into and disrupt the bacterial cell membrane, leading to a decrease in activity.
However, it is also possible that modifying certain amino acids could increase the stability and bioactivity of the AMP. For example, modifying AMPs with lipophilic groups can increase their stability and antimicrobial activity, particularly against Gram-negative bacteria.
Overall, the impact of modifying specific amino acids on the antimicrobial activity of a peptide will depend on the specific modification and the target pathogen. It is important to carefully consider the potential impact of amino acid modifications on antimicrobial activity when designing and developing AMPs for therapeutic use.
Dear Sleiman Bisharat I think the excellent review by Torres et al. is a good starting point in finding an answer to your question:
Synthetic Biology and Computer-Based Frameworks for Antimicrobial Peptide Discovery. Marcelo D. T. Torres, Jicong Cao, Octavio L. Franco, Timothy K. Lu, and Cesar de la Fuente-Nunez. ACS Nano 2021 15 (2), 2143-2164 DOI: 10.1021/acsnano.0c09509