Structural Motifs in Protein Biology

While we've initiated dialogues on integrating AI, it hasn't transformed our work yet. However, I see it as a significant tool, especially for handling and processing big data. AI can help bridge the expertise gap in understanding both bioinformatics and biological terms, aiding in the efficient mining of information.

Having worked across different parts of the discovery process, I think broad exposure changes the way you think. I have developed quantum chemistry, artificial intelligence (AI) and machine learning (ML) methods in research settings, but I have also had the chance to apply them in real discovery environments for materials and pharmaceuticals. That experience has shown me how different parts of the discovery pipeline interact, what their motivations are, and how they communicate. AI and ML have been used in early discovery for many years, but the biggest recent shift is in areas dominated by human processes and communication. Computers can now interact directly with human language and analytical images, opening new applications such as AI research assistants and AI-assisted dossier drafting. That means AI can start to work more collaboratively with scientists, although expert oversight and guardrails remain essential. In nonclinical safety, I think the biggest impact will be AI working alongside safety scientists to unearth key data, connect safety science with earlier discovery and later clinical work, and help process, predict, and summarize important outcomes. That could help safety science integrate more tightly with design, make, and test cycles in discovery, while also interfacing earlier with clinical science. Save a Copy of This Exclusive Interview by Downloading the Free PDF

The pKa for an amino acid is an acid dissociation constant that refers to the equilibrium between the protonated and deprotonated forms of the backbone amino group, backbone carboxyl group, and any potential acid/base component of the variable group. The net charge of the protein is determined by summing the charge of individual amino acids across the protein. pKa relates to the equilibrium constant and defines the transition between two structural forms of an amino acid–protonated and deprotonated. Amino acids possess distinct pKas for the carbonyl group, amino group, and any functional groups on the side chain that may be protonated or deprotonated. There is always one more structure than the number of pKa values for amino acids. For example, if there were two pKa values, three structures can be discerned. This is illustrated below using glycine, which has two pKa values – pKa 1 represents the (de)protonation of the carboxyl group and pKa2 represents the (de)protonation of the amine group: When the pH< pKa protonation of the amino and carboxyl groups occurs, resulting in a net +1 positive charge for glycine. When the pH is increased to a value between the two pKas(pKa2>pH> pKa1), the carboxyl group is deprotonated while the amino group remains protonated. This represents the zwitterionic form of the amino acid as it simultaneously possesses a positive and negative charge. When the pH> pKa2, the amino group is deprotonated and loses its charge. The amino acid now carries a net negative charge of -1. The zwitterionic form of the amino acid can exist at any pH value between pKa1 and pKa2.

Techniques are always evolving and the areas that they are going to be used in are going to be virtually unlimited. Petrochemistry, for example, is just one area, although that is the area of this particular talk. They are just as useful in environmental analysis, food and beverage analysis, fragrance, forensic science. It cuts across all these areas, so the research involving ionic liquids, or using them, can go in any direction.

Carb cycling is an attempt to fine-tune your carbohydrate consumption to alter many aspects of your metabolism. Your plan will include the same protein intake each day but vary carbohydrates according to your activity. Your carb cycling plan may have three low or zero carb days, two moderate carb days, and two high carb days. Meeting your calorie requirements will require including more fats on low-carb days. Carb cycling needs much more planning than a usual calorie-controlled diet. One way is to match your carb cycling to your physical activity. If you go to the gym thrice a week, you could have carbs on those days. The carbs provide energy for your workout, prevent fatigue, and avoid the muscle loss sometimes seen with dieting. The days when you eat little to no carbs force your body to generate energy from other sources, like proteins and fats. But the days when you eat more carbohydrates might reverse this change. You must only eat a high-carb diet on the days you have a heavy workout, which uses up the calories.