SearcharxivSearch

arXiv · 1409.0243

Can we make biochemistry an exact science?

Abstract

Biochemists know that the law of mass action is not exact and not very useful because we cannot transfer it (with unchanged parameters) from one condition to another. I argue that exact equations require calibrated multiscale analysis to deal with ions. Exact theories in biochemistry must use mathematics of interactions because biological ionic solutions, derived from seawater, are complex (not simple) fluids. The activity of one ion depends on every other ion. Mathematics of conservative interactions is well understood but friction is another matter. Mathematicians now have now an energetic variational calculus dealing with friction. Complex fluids need variational methods because everything interacts with everything else. Mathematics designed to handle interactions is needed to produce exact equations. If interactions are not addressed with variational mathematics, they are bewildering. The mathematics must include the global properties of the electric field. Flow of charge in one place changes the flow everywhere by Kirchoff and Maxwell laws. Charge changes physical nature as it flows through a circuit. It is ions in salt water; it is electrons in a vacuum tube; it is quasi-particles in a semiconductor; and it is nothing much in a vacuum capacitor (i.e., displacement current). Charge is abstract. The physical nature of charge and current is strikingly diverse; yet, the flow of current is exactly the same in every element in a series circuit. The global nature of electric flow prevents the law of mass action from being exact. The law of mass action (with rate constants that are constant) does not know about charge. The law of mass action is about mass conservation. I believe the law of mass action must be modified to be consistent with the Kirchoff current law if biochemistry is to be an exact science.

Explore related subjects

Keep this discovery

BibTeXRIS

Bob Eisenberg. 2014-08-31. Can we make biochemistry an exact science?. https://arxiv.org/abs/1409.0243

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

Sequence-Informed Geometric Evaluation of RNA 3D Structures

Computational RNA structure pipelines generate many candidate conformations for the same sequence. Reliable evaluation therefore requires more than recognising plausible geometry, it requires determining whether that geometry is compatible with the sequence. We introduce SIRGE, a sequence-informed geometric evaluator that conditions structural representations on nucleotide embeddings from a pretrained RNA language model. Early results show that SIRGE outperforms established evaluators in Kendall--$\tau$ alignment, Top-1 selection, and Top-3 ranking. Controlled comparisons further show that sequence conditioning corrects errors made by an otherwise matched geometric model and improves target-level rank structure. These findings provide initial evidence that pretrained sequence representations supply ranking information that complements geometric reasoning.

q-bio.BM

PocketVE: Stable and Property-Guided Structure-Based Drug Design with Variance-Exploding Diffusion

Protein-conditioned 3D molecule generation is a central challenge in structure-based drug design, requiring a balance between pocket compatibility, molecular properties, and physical geometry. We propose \textbf{PocketVE}, a protein-pocket-conditioned variance-exploding (VE) diffusion framework that couples stable coordinate denoising with inference-time property guidance. Specifically, PocketVE combines an EDM-style training and sampling setup for 3D denoising, classifier-free guidance for multi-property steering without external property classifiers, and adaptive protein perturbation as a training-time pocket regularizer. Evaluated on CrossDocked2020 under the GenBench3D protocol, PocketVE improves Valid$_{3\text{D}}$ from 58.6 to 80.6 and reduces strain energy from 457.4 to 127.9 relative to its TAGMol architectural baseline, while retaining competitive docking and molecular-property scores under moderate guidance. A guidance-scale study shows that moderate guidance gives a favorable balance between target-related objectives and geometric quality, whereas stronger guidance can degrade geometry and distributional fidelity. Pocket-permutation and PoseCheck diagnostics further support pocket-specific spatial compatibility with reduced steric conflicts. Overall, the results suggest that geometric stability and inference-time property guidance should be considered as coupled design objectives.

q-bio.BM

Predicting directional flexibility in proteins

Predicting protein dynamics is a long-standing problem in computational structural biology. Often, protein function critically depends on local directed motions, such as hinge movements, catalytic loop rearrangements and domain reorientations, which can be characterized by directional flexibility and correlated structural motions of the protein backbone. While Molecular Dynamics (MD) simulations provide an established but often prohibitively expensive approach, recent deep generative models aim to reduce this cost by directly predicting conformational ensembles, emulating MD. However, due to their large size and the need to generate several states until the derived dynamical properties converge, these models remain expensive. In this work, we propose BackFlip-2: a fast SE(3)-equivariant graph neural network trained to directly predict dynamical descriptors, such as directional backbone flexibility and pairwise dynamic correlations, from an equilibrium structure. In a series of experiments, we show that our model matches the accuracy of substantially larger ensemble generation models while being orders of magnitude faster, and demonstrate that the proposed equivariant architecture is especially well-suited for capturing anisotropic motions in proteins. BackFlip-2 model weights, training and inference code are available at https://github.com/graeter-group/backflip.

q-bio.BM