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I'd just like to ask for a little clarification here due to confusion from interdisciplinary studies.

I'm currently reading the 1976 paper related to the recent 2013 Nobel Prize for Chemistry, by 2 of the laureates Warshel and Levitt — Theoretical Studies of Enzymic Reactions: Dielectric, Electrostatic and Steric Stabilisation of the Carbonium Ion in the Reaction of Lysosyme — and have recently been reading into quantum chemistry, as well as studying biochemistry and have had further lectures in Physics to boot.

I'm wondering if the points made here are comparable to points I've heard in mechanics lectures, about a cannonball not being modelled as a quantum object, since every subatomic particle would be too computationally intensive, so a coarse-grain model is used (i.e. Newton's "classical" laws).

I wouldn't be so quick to draw parallels between mechanics lectures and enzyme biochemistry but it seems to be in the language they are using here (see highlights below).

From what I understand (in mechanics) only 3 of the 4 'fundamental forces' (strong, weak, and EM) only strictly apply at the quantum/microscopic scale, and scientists are as it stands struggling to work gravity into the setup. Is this worth considering in this paper - if an enzyme is considered all of a sudden due to its size as a quantum object does this entail ignoring gravity QM now in favour of 'Newtonian', inertial frame-of-reference type mechanics, or considering it in some other 'Newtonian' manner?

The introductory section is as follows (full paper linked above):

The conformation of the enzyme-substrate complex can be adequately studied using empirical energy functions based on the “classical” contributions of bond stretching, bond angle bending, bond twisting, non-bonded interactions, etc. The mechanism and energetics of the enzymic reaction can only be studied using a quantum mechanical approach. Previous quantum mechanical calculations on enzymic reactions have been limited in several respects. In the first place, they deal with an over-simplified model system consisting of only small fractions of the atoms involved in the real enzyme-substrate interaction. Second, all available quantum mechanical methods treat the reaction as if in a vacuum and are, therefore, unable to include the dielectric, which has a very important effect on the energy and charge distribution of the system. This limitation does not depend on the actual quantum mechanical scheme, being equally valid for the simplest Hiickel treatment and most extensive ab initio calculation.

Because the treatment of the whole enzyme-substrate complex quantum mechanically is computationally impossible, it is necessary to simplify the problem and use a hybrid classical/quantum mechanical approach. The method described here considers the whole enzyme-substrate complex: the energy and charge distribution of those atoms that are directly involved in the reaction are evaluated quantum mechanically, while the potential energy surfac e of the rest of the system, including the urrounding solvent, is evaluated classically. An important feature of the method is the treatment of the “dielectric” effect due to both the protein atoms and the surrounding water molecules. Our dielectric model is based on a direct calculation of the electrostatic field due to the dipoles induced by polarizing the protein atoms, and the dipoles induced by orienting the surrounding water molecules. With the inclusion of the microscopic dielectric effect we feel that our model for enzymic reactions includes all the important factors that may contribute to the potential surface of the enzymic reaction. Because we use analytical expressions to evaluate the energy and first derivative with respect to the atomic Cartesian co-ordinates, it is possible to allow the system to relax using a convergent energy minimization method. Here we use the method to study the mechanism of the lysozyme reaction, with particular emphasis on factors contributing to the stabilization of the carbonium ion intermediate. We first outline our theoretical scheme, paying attention to the partition of the potential surface into classical and quantum mechanical parts and to details of the microscopic dielectric model. Then we use the method to investigate factors that contribute to the stabilization of the carbonium ion intermediate and deal with the relative importance of each factor. The effect of steric strain is considered for both the ground and the carbonium states and found to be of minor importance. Electrostatic stabilization is treated at some length with special emphasis on the balance between stabilization by induced dipoles (polarizability) and stabilization by charge- charge interactions. The results demonstrate the importance of electrostatic stabilization for this reaction.

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Where does it say that a Newtonian consideration of gravity is required?

I would say that even when going coarse grain in (bio)chemical reactions, gravity is neglected. This is due that in comparison with electrostatic interactions, they are about 40 times smaller.

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  • $\begingroup$ This press release from the Royal Swedish Academy of Sciences says that 'they managed to make Newton’s classical physics work side-by-side with the fundamentally different quantum physics. Previously, chemists had to choose to use either or.' $\endgroup$ – Louis Maddox Oct 21 '13 at 22:04
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    $\begingroup$ Sure, but that doesn't imply by necessity gravity. That implies that they managed to use quantum mechanics to calculate electronic states and then going to a higher abstraction of physics (classical mechanics) to study the whole molecule. For example, using QM to determine the "elastic" properties of a bond and then using it to determine structure or dynamics of such a bond in conjunction with the rest of the molecule. $\endgroup$ – Ignacio Vergara Kausel Oct 21 '13 at 22:08
  • $\begingroup$ Right, yes I don't think "mechanics" in the paper is referring to classical SUVAT mechanics but rather molecular mechanics (QM/MM), thank you v much for the input, it helps $\endgroup$ – Louis Maddox Oct 21 '13 at 22:54
  • $\begingroup$ Marking this as correct but any more answers are welcome :-) $\endgroup$ – Louis Maddox Oct 21 '13 at 22:55

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